The Anaphase Promoting Complex/Cyclosome (APC/C): A Versatile E3 Ubiquitin Ligase

  • Natalie L. Curtis
  • Victor M. Bolanos-GarciaEmail author
Part of the Subcellular Biochemistry book series (SCBI, volume 93)


In the present chapter we discuss the essential roles of the human E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) in mitosis as well as the emerging evidence of important APC/C roles in cellular processes beyond cell division control such as regulation of genomic integrity and cell differentiation of the nervous system. We consider the potential incipient role of APC/C dysregulation in the pathophysiology of the neurological disorder Alzheimer’s disease (AD). We also discuss how certain Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) viruses take control of the host’s cell division regulatory system through harnessing APC/C ubiquitin ligase activity and hypothesise the plausible molecular mechanisms underpinning virus manipulation of the APC/C. We also examine how defects in the function of this multisubunit protein assembly drive abnormal cell proliferation and lastly argue the potential of APC/C as a promising therapeutic target for the development of innovative therapies for the treatment of chronic malignancies such as cancer.


Anaphase Promoting Complex/Cyclosome (APC/C) E3 ubiquitin ligase Spindle Assembly Checkpoint (SAC) Proteasome Genome instability Mitosis regulation Chromosome segregation Kinetochore 


Amyloid beta




Alzheimer’s disease




Acute Myeloid Leukemia


Anaphase Promoting Complex/Cyclosome


Adult T-cell Leukaemia/Lymphoma


Adenosine Triphosphate


Ataxia Telangiectasia and Rad3-related protein


BRCA1-associated RING domain protein 1


Brain-Specific Kinase 2


Budding uninhibited by benzimidazoles 1


Budding uninhibited by benzimidazoles 3


Budding uninhibited by benzimidazoles Related 1


Chicken Anemia Virus


Chicken Anemia Virus-Apoptin


Cyclic AMP response element Binding Protein


Cell division cycle 5


Cell division cycle 6


Cell division cycle 7


Cell division cycle 20


Cell division cycle 23


Cell division cycle 26


Cell division cycle 27


Cell division cycle 42


Cell division cycle 55




Cadherin 1


Cyclin-dependent kinase


Cyclin-dependent kinase 1


Cyclin-dependent kinase 4


Cyclin-dependent kinase 5


Chromatin licensing and DNA replication factor 1


Centromere-associated Protein E


Centromere-associated Protein F


Checkpoint kinase 1


Chromosome instability and karyogamy protein 1


Casein Kinase 1


Casein Kinase 1 delta


Cytoskeleton-Associated Protein 2


conditional Knockout


Cyclin-dependent kinases regulatory subunit 1


Central Nervous System




Chromosomal Passenger Complex


cryogenic Electron Microscopy


Destruction box


Damaged DNA Binding protein 1


Deoxyribonucleic Acid


deoxyribonucleotide Triphosphate


deoxythymidine Triphosphate




Adenovirus Early region 1A


E2F Transcription Factor 1


E2F Transcription Factor 3


Early region 4 open reading frame 4


Excitatory Amino Acid


Epithelial cell transforming 2


Euchromatic Histone Lysine Methyltransferase 2


Electron Microscopy


Early mitotic inhibitor


Endoplasmic Reticulum


Eyes Absent 1


FANCD2-Associated Nuclease 1


Filaments in between nuclei protein 1


Forkhead box M1


Fizzy-related protein homolog


Gap 1


Gap 2


Glucose-6-Phosphate Dehydrogenase


Granule Cell Progenitors


Glucagon-Like Peptide


Glucagon-Like Peptide-1


Glutaminase 1


Glutamate Receptor 1


Glioblastoma Stem-like Cells




Glutathione disulfide


Human Adenovirus


Hepatitis B Virus


Hepatocellular Carcinoma


Human Cytomegalovirus


Homologous to the E6-AP Carboxyl Terminus


Human Gyrovirus-Apoptin


Hyaluronan-mediated motility receptor


Human Papillomaviruses

Hsl1 from yeast

Histone synthetic lethal 1


Human T-cell Lymphotropic Virus type 1


Hepatoma Up-Regulated Protein


Inhibitor of differentiation 1


Inhibitor of differentiation 2


Intermediate Early


Intermediate protein 72


Intermediate protein 86


IQ motif containing GTPase-Activating Protein 1


Isoleucine Arginine


Janus Kinase


C-Jun N-terminal Kinase




Kinesin family member 18A


Kinetochore scaffold 1




Large T antigen


Long-Term Potentiation




Mitotic arrest deficient 1


Mitotic arrest deficient 2


Mitogen-Activated Protein Kinase


Mitotic Checkpoint Complex




Mediator DNA Damage Checkpoint 1


Mouse Embryonic Fibroblasts


Male germ cell RacGTPase Activating Protein


Modulator of Apoptosis Protein 1


Monopolar spindle 1


messenger RNA


Nicotinamide Adenine Dinucleotide Phosphate


NIMA-related kinase 2A


Neurogenic Differentiation factor 2


Neurofibrillary Tangles


Nuclear Interaction Partner of Alk kinase


Ninein-like protein


N-methyl-D-aspartate Receptors


Neural Progenitor Cells


Nonstructural protein 5A


Nucleolar Spindle–Associated Protein


Orf Virus


Cyclin dependent kinase inhibitor 1


Cyclin dependent kinase inhibitor 1B


Pancreatic Ductal Adenocarcinoma


Premature dissociation of sisters


6-phosphofructo-2-kinase/fructose-2,6-biphosphatase isoform 3


Polo-like kinase 1

PML bodies

Promyelocytic Leukaemia bodies


Protein Phosphatase 2


Pentose-Phosphate Pathway


Retinoblastoma protein


pro-tosyl-l-arginine methyl ester


Postsynaptic Density


Ras-related C3 botulinum toxin substrate 1


Receptor-Associated Protein 80


Ras association domain containing family 1 isoform a


RING-box protein 1


RING-box protein 2


Ras homolog gene family member A


Really Interesting New Gene


Ribonucleic Acid


RNA interference


Rho protein kinase 2


Reactive Oxygen Species




Spindle Assembly Checkpoint

S. cerevisiae

Saccharomyces cerevisiae


Skp1-Cullin-1-F-box protein


Shugoshin 1


SH3 and multiple ankyrin repeat domains protein


small interfering RNA


Sineoculis homeobox homolog 1


S-phase-kinase-associated protein 1


S-phase kinase-associated protein 2


Ski-related novel protein N


Speckle-type POZ Protein


Signal Transducer and Activator of Transcription


Simian Virus 40


Transforming Acidic Coiled-Coil protein 3


Tosyl-l-arginine methyl ester


Testicular Germ Cell Tumours


Transforming Growth Factor beta


Thymidine Kinase


Thymidylate Protein Kinase


TNM classification of malignant tumors


Tetratricopeptide Repeat


Targeting protein for Xklp2


Tribbles homolog 3


Transformation/Transcription domain-Associated protein


Tiny yeast comet 1


Ubiquitin-conjugating enzyme E2 C


Ubiquitin-conjugating enzyme E2 D2


Ubiquitin carboxyl-terminal hydrolase 1


Ubiquitin Specific-processing Protease 37


Whole-Exome Sequencing


  1. Abrieu A, Magnaghi-Jaulin L, Kahana JA, Peter M, Castro A, Vigneron S, Lorca T, Cleveland DW, Labbe JC (2001) Mps1 is a kinetochore-associated kinase essential for the vertebrate mitotic checkpoint. Cell 106:83–93CrossRefPubMedGoogle Scholar
  2. Acquaviva C, Herzog F, Kraft C, Pines J (2004) The anaphase promoting complex/cyclosome is recruited to centromeres by the spindle assembly checkpoint. Nat Cell Biol 6:892–898CrossRefPubMedGoogle Scholar
  3. Ahn J, Kim H, Yoon J, Jang H, Han S, Eun S, Shim H, Kim H, Kim D, Lee J, Lee C, Bae M, Chung K, Jung J, Kim E, Kim S, Chang J, Kim H, Kim J, Lee M, Cho B, Lee J, Bang D (2014) Identification of somatic mutations in EGFR/KRAS/ALK-negative lung adenocarcinoma in never-smokers. Genome Med 6:18CrossRefPubMedPubMedCentralGoogle Scholar
  4. Alfieri C, Chang L, Zhang Z, Yang J, Maslen S, Skehel M, Barford D (2016) Molecular basis of APC/C regulation by the spindle assembly checkpoint. Nature 536:431–436CrossRefPubMedPubMedCentralGoogle Scholar
  5. Alfieri C, Zhang S, Barford D (2017) Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C). Open Biol 7:170204CrossRefPubMedPubMedCentralGoogle Scholar
  6. Alizadeh AA, Eisen MB, Davis RE, Ma C, Lossos IS, Rosenwald A, Boldrick JC, Sabet H, Tran T, Yu X, Powell JI, Yang L, Marti GE, Moore T, Hudson J Jr, Lu L, Lewis DB, Tibshirani R, Sherlock G, Chan WC, Greiner TC, Weisenburger DD, Armitage JO, Warnke R, Levy R, Wilson W, Grever MR, Byrd JC, Botstein D, Brown PO, Staudt LM (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 403:503–511CrossRefPubMedPubMedCentralGoogle Scholar
  7. Almeida A (2012) Regulation of APC/C-Cdh1 and its function in neuronal survival. Mol Neurobiol 46:547–554CrossRefPubMedPubMedCentralGoogle Scholar
  8. Almeida A, Bolaños J, Moreno S (2005) Cdh1/Hct1-APC Is Essential for the survival of postmitotic neurons. J Neurosci 25:8115–8121CrossRefPubMedPubMedCentralGoogle Scholar
  9. Almeida A, Moncada S, Bolaños JP (2004) Nitric oxide switches on glycolysis through the AMP protein kinase and 6-phosphofructo-2-kinase pathway. Nat Cell Biol 6:45–51CrossRefPubMedGoogle Scholar
  10. Amador V, Ge S, Santamaría PG, Guardavaccaro D, Pagano M (2007) APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase. Mol Cell 27:462CrossRefPubMedPubMedCentralGoogle Scholar
  11. Ang XL, Wade Harper J (2005) SCF-mediated protein degradation and cell cycle control. Oncogene 24:2860–2870CrossRefPubMedGoogle Scholar
  12. Aristarkhov A, Eytan E, Moghe A, Admon A, Hershko A, Ruderman JV (1996) E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins. Proc Natl Acad Sci USA 93:4294–4299CrossRefPubMedGoogle Scholar
  13. Arundine M, Tymianski M (2003) Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity. Cell Calcium 34:325–337CrossRefPubMedGoogle Scholar
  14. Aulia S, Tang B (2006) Cdh1-APC/C, cyclin B-Cdc2, and Alzheimer’s disease pathology. Biochem and Biophys Res Comm 339:1–6CrossRefGoogle Scholar
  15. Baek K, Park H, Kang C, Kim S, Jeong S, Hong E, Park J, Sung Y, Suzuki T, Kim C, Lee C (2006) Overexpression of Hepatitis C Virus NS5A protein induces chromosome instability via mitotic cell cycle dysregulation. J Mol Biol 359:22–34CrossRefPubMedGoogle Scholar
  16. Bain M, Sinclair J (2007) The S phase of the cell cycle and its perturbation by human cytomegalovirus. Rev Med Virol 17:423–434CrossRefPubMedGoogle Scholar
  17. Barford D (2011) Structural insights into anaphase-promoting complex function and mechanism. Philos Trans R Soc London B Biol Sci 366:3605–3624CrossRefPubMedGoogle Scholar
  18. Barford D (2015) Understanding the structural basis for controlling chromosome division. Philos Trans A Math Phys Eng Sci 373:pii:20130392CrossRefGoogle Scholar
  19. Baron AP, von Schubert C, Cubizolles F, Siemeister G, Hitchcock M, Mengel A, Schröder J, Fernández-Montalván A, von Nussbaum F, Mumberg D, Nigg EA (2016) Probing the catalytic functions of Bub1 kinase using the small molecule inhibitors BAY-320 and BAY-524. eLife 5. pii:e12187Google Scholar
  20. Bashir T, Dorrello NV, Amador V, Guardavaccaro D, Pagano M (2004) Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase. Nature 428:190–193CrossRefPubMedGoogle Scholar
  21. Bassermann F, Frescas D, Guardavaccaro D, Busino L, Peschiaroli A, Pagano M (2008) The Cdc14B-Cdh1-Plk1 axis controls the G2 DNA-damage-response checkpoint. Cell 134:256–267CrossRefPubMedPubMedCentralGoogle Scholar
  22. Bedford L, Lowe J, Dick LR, Mayer RJ, Brownell JE (2011) Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets. Nat Rev Drug Discov 10:29–46CrossRefPubMedGoogle Scholar
  23. Bellanger S, Blachon S, Mechali F, Bonne-Andrea C, Thierry F (2005) High-risk but not low-risk HPV E2 proteins bind to the APC activators Cdh1 and Cdc20 and cause genomic instability. Cell Cycle 4:1608–1615CrossRefPubMedGoogle Scholar
  24. Benanti J, Matyskiela ME, Morgan DO, Toczyski DP (2009) Functionally distinct isoforms of Cik1 are differentially regulated by APC/C-mediated proteolysis. Mol Cell 33:581–590Google Scholar
  25. Bharadwaj R, Yu H (2004) The spindle checkpoint, aneuploidy, and cancer. Oncogene 23:2016–2027CrossRefPubMedGoogle Scholar
  26. Bhattacharjee B, Renzette N, Kowalik T (2012) Genetic Analysis of cytomegalovirus in malignant gliomas. J Virol 86:6815–6824CrossRefPubMedPubMedCentralGoogle Scholar
  27. Bliss T, Cooke S (2011) Long-term potentiation and long-term depression: a clinical perspective. Clinics 66:3–17CrossRefPubMedPubMedCentralGoogle Scholar
  28. Bobo-Jiménez V, Delgado-Esteban M, Angibaud J, Sánchez-Morán I, de la Fuente A, Yajeya J, Nägerl U, Castillo J, Bolaños J, Almeida A (2017) APC/CCdh1-Rock2 pathway controls dendritic integrity and memory. Proc Natl Acad Sci USA 114:4513–4518CrossRefPubMedGoogle Scholar
  29. Bolanos-Garcia VM, Blundell TL (2011) BUB1 and BUBR1: multifaceted kinases of the cell cycle. Trends Biochem Sci 36:141–150CrossRefPubMedPubMedCentralGoogle Scholar
  30. Boxus M, Willems L (2009) Mechanisms of HTLV-1 persistence and transformation. Br J Cancer 101:1497–1501CrossRefPubMedPubMedCentralGoogle Scholar
  31. Braunstein I, Miniowitz S, Moshe Y, Hershko A (2007) Inhibitory factors associated with anaphase-promoting complex/cylosome in mitotic checkpoint. Proc Natl Acad Sci USA 104:4870–4875CrossRefPubMedGoogle Scholar
  32. Brito D, Rieder C (2006) Mitotic checkpoint slippage in humans occurs via cyclin B destruction in the presence of an active checkpoint. Curr Biol 16:1194–1200CrossRefPubMedPubMedCentralGoogle Scholar
  33. Brito D, Rieder C (2009) The ability to survive mitosis in the presence of microtubule poisons differs significantly between human nontransformed (RPE-1) and cancer (U2OS, HeLa) cells. Cell Motil Cytoskeleton 66:437–447CrossRefPubMedPubMedCentralGoogle Scholar
  34. Britt W (2008) Manifestations of human cytomegalovirus infection: proposed mechanisms of acute and chronic disease. Curr Top Microbiol Immunol 325:417–470PubMedGoogle Scholar
  35. Brune W (2011) Inhibition of programmed cell death by cytomegaloviruses. Virus Res 157:144–150CrossRefPubMedGoogle Scholar
  36. Budhavarapu VN, White ED, Mahanic CS, Chen L, Lin FT, Lin WC (2012) Regulation of E2F1 by APC/C Cdh1 via K11 linkage-specific ubiquitin chain formation. Cell Cycle 11:2030–2038CrossRefPubMedPubMedCentralGoogle Scholar
  37. Burton JL, Solomon MJ (2007) Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint. Genes Dev 21:655–667CrossRefPubMedPubMedCentralGoogle Scholar
  38. Buschhorn BA, Petzold G, Galova M, Dube P, Kraft C, Herzog F, Stark H, Peters JM (2011) Substrate binding on the APC/C occurs between the coactivator Cdh1 and the processivity factor Doc1. Nat Struct Mol Biol 18:6–13CrossRefPubMedGoogle Scholar
  39. Caffarelli N, Fehr A, Yu D (2013) Cyclin A degradation by primate cytomegalovirus protein pUL21a counters its innate restriction of virus replication. PLoS Pathog 9:e1003825CrossRefPubMedPubMedCentralGoogle Scholar
  40. Calabrese V, Scapagnini G, Ravagna A, Colombrita C, Spadaro F, Butterfield DA, Giuffrida Stella AM (2004) Increased expression of heat shock proteins in rat brain during aging: relationship with mitochondrial function and glutathione redox state. Mech Ageing Dev 125:325–335CrossRefPubMedGoogle Scholar
  41. Caposio P, Orloff SL, Streblow DN (2011) The role of cytomegalovirus in angiogenesis. Virus Res 157:204–211CrossRefPubMedGoogle Scholar
  42. Cardozo T, Pagano M (2004) The SCF ubiquitin ligase: insights into a molecular machine. Nat Rev Mol Cell Biol 5:739–751CrossRefPubMedGoogle Scholar
  43. Cardozo T, Pagano M (2007) Wrenches in the works: drug discovery targeting the SCF ubiquitin ligase and APC/C complexes. BMC Biochem 8:S9CrossRefPubMedPubMedCentralGoogle Scholar
  44. Carroll CW, Morgan DO (2005) Enzymology of the anaphase-promoting complex. Methods Enzymol 398:219–230CrossRefPubMedGoogle Scholar
  45. Carter S, Eklund A, Kohane I, Harris L, Szallasi Z (2006) A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet 38:1043–1048CrossRefPubMedGoogle Scholar
  46. Chaabane W, Ghavami S, Małecki A, Łos M (2017) Human Gyrovirus-Apoptin interferes with the cell cycle and induces G2/M arrest prior to apoptosis. Arch Immunol Ther Exp 65:545–552CrossRefGoogle Scholar
  47. Chabes AL, Pfleger CM, Kirschner MW, Thelander L (2003) Mouse ribonucleotide reductase R2 protein: A new target for anaphase-promoting complex-Cdh1-mediated proteolysis. Proc Natl Acad Sci USA 100:3925–3929CrossRefPubMedGoogle Scholar
  48. Chang DZ, Ma Y, Ji B, Liu Y, Hwu P, Abbruzzese JL, Logsdon C, Wang H (2012) Increased CDC20 expression is associated with pancreatic ductal adenocarcinoma differentiation and progression. J Hematol Oncol 5:15CrossRefPubMedPubMedCentralGoogle Scholar
  49. Chang L, Zhang Z, Yang J, McLaughlin S, Barford D (2015) Atomic structure of the APC/C and its mechanism of protein ubiquitination. Nature 522:450–454CrossRefPubMedPubMedCentralGoogle Scholar
  50. Chang LF, Zhang Z, Yang J, McLaughlin SH, Barford D (2014) Molecular architecture and mechanism of the anaphase-promoting complex. Nature 513:388–393CrossRefPubMedPubMedCentralGoogle Scholar
  51. Chao W, Kulkarni K, Zhang Z, Kong E, Barford D (2012) Structure of the mitotic checkpoint complex. Nature 484:208–213CrossRefPubMedGoogle Scholar
  52. Chen X, Cheung ST, So S, Fan ST, Barry C, Higgins J, Lai KM, Ji J, Dudoit S, Ng IO, Van De Rijn M, Botstein D, Brown PO (2002) Gene expression patterns in human liver cancers. Mol Biol Cell 13:1929–1939CrossRefPubMedPubMedCentralGoogle Scholar
  53. Cho HJ, Lee EH, Han SH, Chung HJ, Jeong JH, Kwon J, Kim H (2012) Degradation of human RAP80 is cell cycle regulated by Cdc20 and Cdh1 ubiquitin ligases. Mol Cancer Res 10:615–625CrossRefPubMedGoogle Scholar
  54. Choi JW, Kim Y, Lee JH, Kim YS (2013) High expression of spindle assembly checkpoint proteins CDC20 and MAD2 is associated with poor prognosis in urothelial bladder cancer. Virchows Arch 463:681–687CrossRefPubMedGoogle Scholar
  55. Chow C, Wong N, Pagano M, Lun SW, Nakayama KI, Nakayama K, Lo KW (2012) Regulation of APC/CCdc20 activity by RASSF1A-APC/CCdc20 circuitry. Oncogene 31:1975–1987CrossRefPubMedGoogle Scholar
  56. Christensen KL, Brennan JD, Aldridge CS, Ford HL (2007) Cell cycle regulation of the human Six1 homeoprotein is mediated by APC(Cdh1). Oncogene 26:3406–3414CrossRefPubMedGoogle Scholar
  57. Chun AC, Kok KH, Jin DY (2013) REV7 is required for anaphase-promoting complex-dependent ubiquitination and degradation of translation DNA polymerase REV1. Cell Cycle 12:365–378CrossRefPubMedPubMedCentralGoogle Scholar
  58. Chung E, Chen RH (2003) Phosphorylation of Cdc20 is required for its inhibition by the spindle checkpoint. Nat Cell Biol 5:748–753CrossRefPubMedGoogle Scholar
  59. Chung E, Chen RH (2002) Spindle checkpoint requires Mad1-bound and Mad1-free Mad2. Mol Biol Cell 13:1501–1511CrossRefPubMedPubMedCentralGoogle Scholar
  60. Ciosk R, Zachariae W, Michaelis C, Shevchenko A, Mann M, Nasmyth K (1998) An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast. Cell 93:1067–1076CrossRefPubMedGoogle Scholar
  61. Ciossani G, Overlack K, Petrovic A, Huis In’t Veld PJ, Koerner C, Wohlgemuth S, Maffini S, Musacchio A (2018) The kinetochore proteins CENP-E and CENP-F directly and specifically interact with distinct BUB mitotic checkpoint Ser/Thr kinases. J Biol Chem 293:10084–10101Google Scholar
  62. Clark E, Spector D (2015) Studies on the contribution of human cytomegalovirus UL21a and UL97 to viral growth and inactivation of the anaphase-promoting complex/cyclosome (APC/C) E3 ubiquitin ligase reveal a unique cellular mechanism for downmodulation of the APC/C subunits APC1, APC4, and APC5. J Virol 89:6928–6939CrossRefPubMedPubMedCentralGoogle Scholar
  63. Clute P, Pines J (1999) Temporal and spatial control of cyclin B1 destruction in metaphase. Nat Cell Biol 1:82–87CrossRefPubMedGoogle Scholar
  64. Cohen-Fix O, Peters JM, Kirschner MW, Koshland D (1996) Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p. Genes Dev 10:3081–3093CrossRefPubMedGoogle Scholar
  65. Colombo SL, Palacios-Callender M, Frakich N, Carcamo S, Kovacs I, Tudzarova S, Moncada S (2011) Molecular basis for the differential use of glucose and glutamine in cell proliferation as revealed by synchronized HeLa cells. Proc Natl Acad Sci USA 108:21069–21074CrossRefPubMedGoogle Scholar
  66. Coster G, Hayouka Z, Argaman L, Strauss C, Friedler A, Brandeis M, Goldberg M (2007) The DNA damage response mediator MDC1 directly interacts with the anaphase-promoting complex/cyclosome. J Biological Chem 282:32053–32064CrossRefGoogle Scholar
  67. Cotsiki M, Lock R, Cheng Y, Williams G, Zhao J, Perera D, Freire R, Entwistle A, Golemis E, Roberts T, Jat P, Gjoerup O (2004) Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1. Proc Nat Acad Sci USA 101:947–952CrossRefPubMedGoogle Scholar
  68. Cotto-Rios XM, Jones MJ, Busino L, Pagano M, Huang TT (2011) APC/CCdh1-dependent proteolysis of USP1 regulates the response to UV-mediated DNA damage. J Cell Biol 194:177–186CrossRefPubMedPubMedCentralGoogle Scholar
  69. Craney A, Kelly A, Jia L, Fedrigo I, Yu H, Rape M (2016) Control of APC/C-dependent ubiquitin chain elongation by reversible phosphorylation. Proc Nat Acad Sci USA 113:1540–1545CrossRefPubMedGoogle Scholar
  70. Crawford L, Anderson G, Johnston C, Irvine A (2016) Identification of the APC/C co-factor FZR1 as a novel therapeutic target for multiple myeloma. Oncotarget 7:70481–70493CrossRefPubMedPubMedCentralGoogle Scholar
  71. Cui Y, Cheng X, Zhang C, Zhang Y, Li S, Wang C, Guadagno TM (2010) Degradation of the human mitotic checkpoint kinase Mps1 is cell cycle-regulated by APC-cCdc20 and APC-cCdh1 ubiquitin ligases. J Biol Chem 285:32988–32998CrossRefPubMedPubMedCentralGoogle Scholar
  72. da Fonseca PC, Kong EH, Zhang Z, Schreiber A, Williams MA, Morris EP, Barford D (2011) Structures of APC/C(Cdh1) with substrates identify Cdh1 and Apc10 as the D-box co-receptor. Nature 470:274–278CrossRefPubMedGoogle Scholar
  73. Danen-van Oorschot A, Zhang Y, Leliveld S, Rohn J, Seelen M, Bolk M, van Zon A, Erkeland S, Abrahams J, Mumberg D, Noteborn M (2003) Importance of nuclear localization of apoptin for tumor-specific induction of apoptosis. J Biol Chem 278:27729–27736CrossRefPubMedGoogle Scholar
  74. De Antoni A, Pearson CG, Cimini D, Canman JC, Sala V, Nezi L, Mapelli M, Sironi L, Faretta M, Salmon ED, Musacchio A (2005) The Mad1/Mad2 complex as a template for Mad2 activation in the spindle assembly checkpoint. Curr Biol 15:214–225CrossRefPubMedGoogle Scholar
  75. de Boer H, Guerrero Llobet S, van Vugt M (2015) Controlling the response to DNA damage by the APC/C-Cdh1. Cell Mol Life Sci 73:949–960CrossRefPubMedPubMedCentralGoogle Scholar
  76. DeCaprio J (2009) How the Rb tumor suppressor structure and function was revealed by the study of Adenovirus and SV40. Virol 384:274–284CrossRefGoogle Scholar
  77. De Felice F, Velasco P, Lambert M, Viola K, Fernandez S, Ferreira S, Klein W (2007) Aβ oligomers induce neuronal oxidative stress through an N-Methyl-D-aspartate receptor-dependent mechanism that is blocked by the alzheimer drug memantine. J Biol Chem 282:11590–11601CrossRefPubMedGoogle Scholar
  78. Delgado-Esteban M, García-Higuera I, Maestre C, Moreno S, Almeida A (2013) APC/C-Cdh1 coordinates neurogenesis and cortical size during development. Nat Commun 4:2879CrossRefPubMedGoogle Scholar
  79. den Elzen N, Pines J (2001) Cyclin A is destroyed in prometaphase and can delay chromosome alignment and anaphase. J Cell Biol 153:121–136CrossRefGoogle Scholar
  80. Derive N, Landmann C, Montembault E, Claverie M, Pierre-Elies P, Goutte-Gattat D, Founounou N, McCusker D, Royou A (2015) Bub3–BubR1-dependent sequestration of Cdc20 Fizzy at DNA breaks facilitates the correct segregation of broken chromosomes. J Cell Biol 211:517–532CrossRefPubMedPubMedCentralGoogle Scholar
  81. Deshaies RJ, Joazeiro CA (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78:399–434CrossRefPubMedGoogle Scholar
  82. Diaz-Martinez LA, Tian W, Li B, Warrington R, Jia L, Brautigam CA, Luo X, Yu H (2015) The Cdc20-binding Phe box of the spindle checkpoint protein BubR1 maintains the mitotic checkpoint complex during mitosis. J Biol Chem 290:2431–2443CrossRefPubMedGoogle Scholar
  83. Di Fiore B, Davey NE, Hagting A, Izawa D, Mansfeld J, Gibson TJ, Pines J (2015) The ABBA motif binds APC/C activators and is shared by APC/C substrates and regulators. Dev Cell 32:358–372CrossRefPubMedPubMedCentralGoogle Scholar
  84. Di Fiore B, Wurzenberger C, Davey NE, Pines J (2016) The mitotic checkpoint complex requires an evolutionary conserved cassette to bind and inhibit active APC/C. Mol Cell 64:1144–1153CrossRefPubMedPubMedCentralGoogle Scholar
  85. Ding ZY, Wu HR, Zhang JM, Huang GR, Ji DD (2014) Expression characteristics of CDC20 in gastric cancer and its correlation with poor prognosis. Int J of Cli Exp Pathol 7:722–727Google Scholar
  86. Dong S, Huang F, Zhang H, Chen Q (2019) Overexpression of BUB1B, CCNA2, CDC20, and CDK1 in tumor tissues predicts poor survival in pancreatic ductal adenocarcinoma. Biosci Rep 39:BSR20182306Google Scholar
  87. Dong X, Wang Y, Qin Z (2009) Molecular mechanisms of excitotoxicity and their relevance to pathogenesis of neurodegenerative diseases. Acta Pharmacol Sin 30:379–387CrossRefPubMedPubMedCentralGoogle Scholar
  88. Donzelli M, Squatrito M, Ganoth D, Hershko A, Pagano M, Draetta GF (2002) Dual mode of degradation of Cdc25 A phosphatase. EMBO J 21:4875–4884CrossRefPubMedPubMedCentralGoogle Scholar
  89. Drouet Y, Treilleux I, Viari A, Léon S, Devouassoux-Shisheboran M, Voirin N, de la Fouchardière C, Manship B, Puisieux A, Lasset C, Moyret-Lalle C (2018) Integrated analysis highlights APC11 protein expression as a likely new independent predictive marker for colorectal cancer. Sci Rep 8:7386CrossRefPubMedPubMedCentralGoogle Scholar
  90. Engelbert D, Schnerch D, Baumgarten A, Wäsch R (2007) The ubiquitin ligase APCCdh1 is required to maintain genome integrity in primary human cells. Oncogene 27:907–917CrossRefPubMedGoogle Scholar
  91. Enquist-Newman M, Sullivan M, Morgan DO (2008) Modulation of the mitotic regulatory network by APC-dependent destruction of the Cdh1 inhibitor Acm1. Mol Cell 30:437–446CrossRefPubMedPubMedCentralGoogle Scholar
  92. Fehr A, Gualberto N, Savaryn J, Terhune S, Yu D (2012) Proteasome-dependent disruption of the E3 ubiquitin ligase anaphase-promoting complex by HCMV protein pUL21a. PLoS Pathog 8:e1002789CrossRefPubMedPubMedCentralGoogle Scholar
  93. Fehr A, Yu D (2013) Control the host cell cycle: viral regulation of the anaphase-promoting complex. J Virol 87:8818–8825CrossRefPubMedPubMedCentralGoogle Scholar
  94. Fehr A, Yu D (2010) Human cytomegalovirus early protein pUL21a promotes efficient viral DNA synthesis and the late accumulation of immediate-early transcripts. J Virol 85:663–674CrossRefPubMedPubMedCentralGoogle Scholar
  95. Fehr A, Yu D (2009) Human cytomegalovirus gene UL21a Encodes a short-lived cytoplasmic protein and facilitates virus replication in fibroblasts. J Virol 84:291–302CrossRefPubMedCentralGoogle Scholar
  96. Feine O, Zur A, Mahbubani H, Brandeis M (2007) Human Kid is degraded by the APC/C(Cdh1) but not by the APC/C(Cdc20). Cell Cycle 6:2516–2523Google Scholar
  97. Fleming S, Wise L, Mercer A (2015) Molecular genetic analysis of orf virus: a poxvirus that has adapted to skin. Viruses 7:1505–1539CrossRefPubMedPubMedCentralGoogle Scholar
  98. Foe I, Toczyski D (2011) Structural biology: a new look for the APC. Nature 470:182–183CrossRefPubMedGoogle Scholar
  99. Fonseca R, Vabulas RM, Hartl FU, Bonhoeffer T, Nagerl UV (2006) A balance of protein synthesis and proteasome-dependent degradation determines the maintenance of LTP. Neuron 52:239–245CrossRefPubMedGoogle Scholar
  100. Fortunato EA, Dell’Aquila ML, Spector DH (2000) Specific chromosome 1 breaks induced by human cytomegalovirus. Proc Natl Acad Sci USA 97:853–858CrossRefPubMedGoogle Scholar
  101. Frye JJ, Brown NG, Petzold G, Watson ER, Grace CR, Nourse A, Jarvis MA, Kriwacki RW, Peters JM, Stark H, Schulman BA (2013) Electron microscopy structure of human APC/C(CDH1)-EMI1 reveals multimodal mechanism of E3 ligase shutdown. Nat Struct Mol Biol 20:827–835CrossRefPubMedPubMedCentralGoogle Scholar
  102. Fu AK, Hung KW, Fu WY, Shen C, Chen Y, Xia J, Lai KO, Ip NY (2011) APC(Cdh1) mediates EphA4-dependent downregulation of AMPA receptors in homeostatic plasticity. Nat Neurosci 14:181–189CrossRefPubMedGoogle Scholar
  103. Fuchsberger T, Lloret A, Viña J (2017) New functions of APC/C ubiquitin ligase in the nervous system and its role in alzheimer’s disease. Int J Mol Sci 18:pii:E1057CrossRefPubMedCentralGoogle Scholar
  104. Fuchsberger T, Martínez-Bellver S, Giraldo E, Teruel-Martí V, Lloret A, Viña J (2016) Aβ induces excitotoxicity mediated by APC/C-Cdh1 depletion that can be prevented by glutaminase inhibition promoting neuronal survival. Sci Rep 6:31158CrossRefPubMedPubMedCentralGoogle Scholar
  105. Fujita T, Liu W, Doihara H, Date H, Wan Y (2008a) Dissection of the APCCdh1-Skp2 cascade in breast cancer. Clin Cancer Res 14:1966–1975CrossRefPubMedGoogle Scholar
  106. Fujita T, Liu W, Doihara H, Wan Y (2008b) Regulation of Skp2-p27 Axis by the Cdh1/anaphase-promoting complex pathway in colorectal tumorigenesis. Am J Pathol 173:217–228CrossRefPubMedPubMedCentralGoogle Scholar
  107. Gao D, Inuzuka H, Korenjak M, Tseng A, Wu T, Wan L, Kirschner M, Dyson N, Wei W (2009) Cdh1 regulates cell cycle through modulating the claspin/Chk1 and the Rb/E2F1 pathways. Mol Biol Cell 20:3305–3316CrossRefPubMedPubMedCentralGoogle Scholar
  108. Gao Y, Zhang B, Wang Y, Shang G (2018) Cdc20 inhibitor apcin inhibits the growth and invasion of osteosarcoma cells. Oncol Rep 40:841–848PubMedGoogle Scholar
  109. Garber ME, Troyanskaya OG, Schluens K, Petersen S, Thaesler Z, Pacyna-Gengelbach M, van de Rijn M, Rosen GD, Perou CM, Whyte RI, Altman RB, Brown PO, Botstein D, Petersen I (2001) Diversity of gene expression in adenocarcinoma of the lung. Proc Nat Acad Sci USA 98:13784–13789CrossRefPubMedGoogle Scholar
  110. García-Higuera I, Manchado E, Dubus P, Cañamero M, Méndez J, Moreno S, Malumbres M (2008) Genomic stability and tumour suppression by the APC/C cofactor Cdh1. Nat Cell Biol 10:802–811CrossRefPubMedGoogle Scholar
  111. Gascoigne K, Taylor S (2009) How do anti-mitotic drugs kill cancer cells? J Cell Sci 122:2579–2585CrossRefPubMedGoogle Scholar
  112. Geley S, Kramer E, Gieffers C, Gannon J, Peters JM, Hunt T (2001) Anaphase-promoting complex/cyclosome-dependent proteolysis of human cyclin A starts at the beginning of mitosis and is not subject to the spindle assembly checkpoint. J Cell Biol 153:137–148CrossRefPubMedPubMedCentralGoogle Scholar
  113. Gella A, Durany N (2009) Oxidative stress in Alzheimer disease. Cell Adh Migr 3:88–93CrossRefPubMedPubMedCentralGoogle Scholar
  114. Giovinazzi S, Bellapu D, Morozov V, Ishov A (2013) Targeting mitotic exit with hyperthermia or APC/C inhibition to increase paclitaxel efficacy. Cell Cycle 12:2598–2607CrossRefPubMedPubMedCentralGoogle Scholar
  115. Glotzer M, Murray AW, Kirschner MW (1991) Cyclin is degraded by the ubiquitin pathway. Nature 349:132–138CrossRefPubMedGoogle Scholar
  116. Goodman RH, Smolik S (2000) CBP/p300 in cell growth, transformation and development. Genes Dev 14:1553–1577PubMedGoogle Scholar
  117. Grabsch H, Takeno S, Parsons WJ, Pomjanski N, Boecking A, Gabbert HE, Mueller W (2003) Overexpression of the mitotic checkpoint genes BUB1, BUBR1, and BUB3 in gastric cancer-association with tumour cell proliferation. J Pathol 200:16–22CrossRefPubMedGoogle Scholar
  118. Gujar A, Yano H, Kim A (2015) The CDC20-APC/SOX2 signaling axis: an achilles’ heel for glioblastoma. Mol Cellular Oncol 3:pe.1075644Google Scholar
  119. Gurden MD, Holland AJ, van Zon W, Tighe A, Vergnolle MA, Andres DA, Spielmann HP, Malumbres M, Wolthuis RM, Cleveland DW, Taylor SS (2010) Cdc20 is required for the post-anaphase, KEN-dependent degradation of centromere protein F. J Cell Sci 123:321–330CrossRefPubMedPubMedCentralGoogle Scholar
  120. Gütgemann I, Lehman NL, Jackson PK, Longacre TA (2008) Emi1 protein accumulation implicates misregulation of the anaphase promoting complex/cyclosome pathway in ovarian clear cell carcinoma. Mod Pathol 21:445–454CrossRefPubMedGoogle Scholar
  121. Gutierrez GJ, Tsuji T, Chen M, Jiang W, Ronai ZA (2010) Interplay between Cdh1 and JNK activity during the cell cycle. Nat Cell Biol 12:686–695CrossRefPubMedPubMedCentralGoogle Scholar
  122. Hagting A, Den Elzen N, Vodermaier HC, Waizenegger IC, Peters JM, Pines J (2002) Human securin proteolysis is controlled by the spindle checkpoint and reveals when the APC/C switches from activation by Cdc20 to Cdh1. J Cell Biol 157:1125–1137CrossRefPubMedPubMedCentralGoogle Scholar
  123. Hames RS, Wattam SL, Yamano H, Bacchieri R, Fry AM (2001) APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box. EMBO J 20:7117–7127CrossRefPubMedPubMedCentralGoogle Scholar
  124. Hardwick KG, Weiss E, Luca FC, Winey M, Murray AW (1996) Activation of the budding yeast spindle assembly checkpoint without mitotic spindle disruption. Science 273:953–956CrossRefPubMedGoogle Scholar
  125. Harley ME, Allan LA, Sanderson HS, Clarke PR (2010) Phosphorylation of Mcl-1 by CDK1-cyclin B1 initiates its Cdc20-dependent destruction during mitotic arrest. EMBO J 29:2407–2420CrossRefPubMedPubMedCentralGoogle Scholar
  126. Harper JW, Burton JL, Solomon MJ (2002) The anaphase-promoting complex: it’s not just for mitosis any more. Genes Dev 16:2179–2206CrossRefPubMedGoogle Scholar
  127. Hayes MJ, Kimata Y, Wattam SL, Lindon C, Mao G, Yamano H, Fry AM (2006) Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with the APC/C. Nat Cell Biol 8:607–614CrossRefPubMedGoogle Scholar
  128. He J, Chao WC, Zhang Z, Yang J, Cronin N, Barford D (2013) Insights into degron recognition by APC/C coactivators from the structure of an Acm1-Cdh1 complex. Mol Cell 50:649–656CrossRefPubMedPubMedCentralGoogle Scholar
  129. Heighway J, Knapp T, Boyce L, Brennand S, Field JK, Betticher DC, Ratschiller D, Gugger M, Donovan M, Lasek A, Rickert P (2002) Expression profiling of primary non-small cell lung cancer for target identification. Oncogene 21:7749–7763CrossRefPubMedGoogle Scholar
  130. Heilman D, Teodoro J, Green M (2006) Apoptin nucleocytoplasmic shuttling is required for cell type-specific localization, apoptosis, and recruitment of the anaphase-promoting complex/cyclosome to PML bodies. J Virol 80:7535–7545CrossRefPubMedPubMedCentralGoogle Scholar
  131. Hein J, Boichuk S, Wu J, Cheng Y, Freire R, Jat P, Roberts T, Gjoerup O (2008) Simian virus 40 large T antigen disrupts genome integrity and activates a DNA damage response via Bub1 binding. J Virol 83:117–127CrossRefPubMedPubMedCentralGoogle Scholar
  132. Hein JB, Hertz EPT, Garvanska DH, Kruse T, Nilsson J (2017) Distinct kinetics of serine and threonine dephosphorylation are essential for mitosis. Nat Cell Biol 19:1433–1440CrossRefPubMedPubMedCentralGoogle Scholar
  133. Hein JB, Nilsson J (2014) Stable MCC binding to the APC/C is required for a functional spindle assembly checkpoint. EMBO Rep 15:264–272CrossRefPubMedPubMedCentralGoogle Scholar
  134. Hernando E, Nahle Z, Juan G, Diaz-Rodriguez E, Alaminos M, Hemann M, Michel L, Mittal V, Gerald W, Benezra R (2004) Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control. Nature 430:797–802CrossRefPubMedPubMedCentralGoogle Scholar
  135. Herrero-Mendez A, Almeida A, Fernández E, Maestre C, Moncada S, Bolaños J (2009) The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C–Cdh1. Nat Cell Biol 11:747–752CrossRefPubMedPubMedCentralGoogle Scholar
  136. Hewitt L, Tighe A, Santaguida S, White A, Jones C, Musacchio A, Green S, Taylor S (2010) Sustained Mps1 activity is required in mitosis to recruit O-Mad2 to the Mad1–C-Mad2 core complex. J Cell Biol 190:25–34CrossRefPubMedPubMedCentralGoogle Scholar
  137. Hisaoka M, Matsuyama A, Hashimoto H (2008) Aberrant MAD2 expression in soft-tissue sarcoma. Pathol Int 58:329–333CrossRefPubMedPubMedCentralGoogle Scholar
  138. Höckner S, Neumann-Arnold L, Seufert W (2016) Dual control by Cdk1 phosphorylation of the budding yeast APC/C ubiquitin ligase activator Cdh1. Mol Biol Cell 27:2198–2212CrossRefPubMedPubMedCentralGoogle Scholar
  139. Hsu JY, Reimann JD, Sørensen CS, Lukas J, Jackson PK (2002) E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1). Nat Cell Biol 4:358–366CrossRefPubMedPubMedCentralGoogle Scholar
  140. Hu K, Liao D, Wu W, Han A, Shi H, Wang F, Wang X, Zhong L, Duan T, Wu Y, Cao J, Tang J, Sang Y, Wang L, Lv X, Xu S, Zhang R, Deng W, Li S, Zeng Y, Kang T (2014) Targeting the anaphase-promoting complex/cyclosome (APC/C)- bromodomain containing 7 (BRD7) pathway for human osteosarcoma. Oncotarget 5:3088–3100PubMedPubMedCentralGoogle Scholar
  141. Hu D, Qiao X, Wu G, Wan Y (2011) The emerging role of APC/CCdh1 in development. Semin Cell Dev Biol 22:579–585CrossRefPubMedPubMedCentralGoogle Scholar
  142. Huang JN, Park I, Ellingson E, Littlepage LE, Pellman D (2001) Activity of the APC(Cdh1) form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p. J Cell Biol 154:85–94CrossRefPubMedPubMedCentralGoogle Scholar
  143. Huang H, Shi J, Orth J, Mitchison T (2009) Evidence that mitotic exit is a better cancer therapeutic target than spindle assembly. Cancer Cell 16:347–358CrossRefPubMedPubMedCentralGoogle Scholar
  144. Huang NJ, Zhang L, Tang W, Chen C, Yang CS, Kornbluth S (2012) The Trim39 ubiquitin ligase inhibits APC/CCdh1-mediated degradation of the Bax activator MOAP-1. J Cell Biol 197:361–367CrossRefPubMedPubMedCentralGoogle Scholar
  145. Huang W, Zhang X, Chen W (2016) Role of oxidative stress in Alzheimer’s disease. Biomed Rep 4:519–522CrossRefPubMedPubMedCentralGoogle Scholar
  146. Hume A, Finkel J, Kamil J, Coen D, Culbertson M, Kalejta R (2008) Phosphorylation of retinoblastoma protein by viral protein with cyclin-dependent kinase function. Science 320:797–799CrossRefGoogle Scholar
  147. Hume AJ, Kalejta RF (2009) Regulation of the retinoblastoma proteins by the human herpesviruses. Cell Div 4:1CrossRefPubMedPubMedCentralGoogle Scholar
  148. Hyun SY, Sarantuya B, Lee HJ, Jang YJ (2013) APC/C(Cdh1)-dependent degradation of Cdc20 requires a phosphorylation on CRY-box by Polo-like kinase-1 during somatic cell cycle. Biochem Biophys Res Comm 436:12–18CrossRefGoogle Scholar
  149. Ichim G, Mola M, Finkbeiner MG, Cros MP, Herceg Z, Hernandez-Vargas H (2014) The histone acetyltransferase component TRRAP is targeted for destruction during the cell cycle. Oncogene 33:181–192CrossRefGoogle Scholar
  150. Irniger S, Nasmyth K (1997) The anaphase-promoting complex is required in G1 arrested yeast cells to inhibit B-type cyclin accumulation and to prevent uncontrolled entry into S-phase. J Cell Sci 110:1523–1531PubMedPubMedCentralGoogle Scholar
  151. Izawa D, Pines J (2012) Mad2 and the APC/C compete for the same site on Cdc20 to ensure proper chromosome segregation. J Cell Biol 199:27–37CrossRefPubMedPubMedCentralGoogle Scholar
  152. Izawa D, Pines J (2015) The mitotic checkpoint complex binds a second CDC20 to inhibit active APC/C. Nature 517:631–634CrossRefPubMedPubMedCentralGoogle Scholar
  153. Jeng JC, Lin YM, Lin CH, Shih HM (2009) Cdh1 controls the stability of TACC3. Cell Cycle 8:3537–3544Google Scholar
  154. Jin J, Cardozo T, Lovering RC, Elledge SJ, Pagano M, Harper JW (2004) Systematic analysis and nomenclature of mammalian F-box proteins. Genes Dev 18:2573–2580CrossRefPubMedPubMedCentralGoogle Scholar
  155. Jordan M, Wilson L (2004) Microtubules as a target for anticancer drugs. Nat Rev Cancer 4:253–265CrossRefPubMedPubMedCentralGoogle Scholar
  156. Juhlin C, Goh G, Healy J, Fonseca A, Scholl U, Stenman A, Kunstman J, Brown T, Overton J, Mane S, Nelson-Williams C, Bäckdahl M, Suttorp A, Haase M, Choi M, Schlessinger J, Rimm D, Höög A, Prasad M, Korah R, Larsson C, Lifton R, Carling T (2015) Whole-exome sequencing characterizes the landscape of somatic mutations and copy number alterations in adrenocortical carcinoma. J Clin Endocrinol Metab 100:E493–E502CrossRefPubMedPubMedCentralGoogle Scholar
  157. Kapanidou M, Bolanos-Garcia V (2014) Spindle assembly checkpoint (SAC): more new targets for anti-cancer drug therapies. Adv Cancer Drug Targets 2:54–79Google Scholar
  158. Kapanidou M, Curtis N, Bolanos-Garcia V (2017) Cdc20: at the crossroads between chromosome segregation and mitotic exit. Trends Biochem Sci 42:193–205CrossRefPubMedPubMedCentralGoogle Scholar
  159. Kapanidou M, Lee S, Bolanos-Garcia V (2015) BubR1 kinase: protection against aneuploidy and premature aging. Trends Mol Med 21:364–372CrossRefPubMedPubMedCentralGoogle Scholar
  160. Karamysheva Z, Diaz-Martinez LA, Crow SE, Li B, Yu H (2009) Multiple anaphase-promoting complex/cyclosome degrons mediate the degradation of human Sgo1. J Biol Chem 284:1772–1780Google Scholar
  161. Karra H, Repo H, Ahonen I, Loyttyniemi E, Pitkanen R, Lintunen M, Kuopio T, Soderstrom M, Kronqvist P (2014) Cdc20 and securin overexpression predict short-term breast cancer survival. Brit J Cancer 110:2905–2913CrossRefPubMedPubMedCentralGoogle Scholar
  162. Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kaji M (2012) Overexpression of CDC20 predicts poor prognosis in primary non-small cell lung cancer patients. J Surg Oncol 106:423–430CrossRefPubMedPubMedCentralGoogle Scholar
  163. Kato T, Daigo Y, Aragaki M, Ishikawa K, Sato M, Kondo S, Kaji M (2011) Overexpression of MAD2 predicts clinical outcome in primary lung cancer patients. Lung Cancer 74:124–131CrossRefPubMedPubMedCentralGoogle Scholar
  164. Ke PY, Chang ZF (2004) Mitotic degradation of human thymidine kinase 1 is dependent on the anaphase-promoting complex/cyclosome-CDH1-mediated pathway. Mol Cell Biol 24:514–526CrossRefPubMedPubMedCentralGoogle Scholar
  165. Ke PY, Hu CM, Chang YC, Chang ZF (2007) Hiding human thymidine kinase 1 from APC/C-mediated destruction by thymidine binding. FASEB J 21:1276–1284CrossRefPubMedPubMedCentralGoogle Scholar
  166. Ke PY, Kuo YY, Hu CM, Chang ZF (2005) Control of dTTP pool size by anaphase promoting complex/cyclosome is essential for the maintenance of genetic stability. Genes Dev 19:1920–1933CrossRefPubMedPubMedCentralGoogle Scholar
  167. Kim Y, Choi JW, Lee JH, Kim YS (2014) MAD2 and CDC20 are upregulated in high-grade squamous intraepithelial lesions and squamous cell carcinomas of the uterine cervix. Int J Gynecol Pathol 33:517–523CrossRefPubMedPubMedCentralGoogle Scholar
  168. Kim S, Park S, Yong H, Famulski J, Chae S, Lee J, Kang C, Saya H, Chan G, Cho H (2008) HBV X protein targets hBubR1, which induces dysregulation of the mitotic checkpoint. Oncogene 27:3457–3464CrossRefPubMedPubMedCentralGoogle Scholar
  169. Kim AH, Puram SV, Bilimoria PM, Ikeuchi Y, Keough S, Wong M, Rowitch D, Bonni A (2009) A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons. Cell 136:322–336CrossRefPubMedPubMedCentralGoogle Scholar
  170. Kimata Y, Trickey M, Izawa D, Gannon J, Yamamoto M, Yamano H (2008) A mutual inhibition between APC/C and its substrate Mes1 required for meiotic progression in fission yeast. Dev Cell 14:446–454CrossRefPubMedPubMedCentralGoogle Scholar
  171. Kleinberger T (2015) Mechanisms of cancer cell killing by the adenovirus E4orf4 protein. Viruses 7:2334–2357CrossRefPubMedPubMedCentralGoogle Scholar
  172. Klitzing CV, Huss R, Illert AL, Fröschl A, Wötzel S, Peschel C, Bassermann F, Duyster J (2011) APC/C(Cdh1)-mediated degradation of the F-box protein NIPA is regulated by its association with Skp1. PLoS ONE 6:e28998CrossRefPubMedPubMedCentralGoogle Scholar
  173. Ko N, Nishihama R, Tully GH, Ostapenko D, Solomon MJ, Morgan DO, Pringle JR (2007) Identification of yeast IQGAP (Iqg1p) as an anaphase-promoting-complex substrate and its role in actomyosin-ring-independent cytokinesis. Mol Biol Cell 18:5139–5153CrossRefPubMedPubMedCentralGoogle Scholar
  174. Komander D, Rape M (2012) The ubiquitin code. Ann Rev Biochem 81:203–229CrossRefPubMedGoogle Scholar
  175. Konishi Y, Stegmuller J, Matsuda T, Bonni S, Bonni A (2004) Cdh1-APC controls axonal growth and patterning in the mammalian brain. Science 303:1026–1030CrossRefPubMedGoogle Scholar
  176. Kornitzer D, Sharf R, Kleinberger T (2001) Adenovirus E4orf4 protein induces PP2A-dependent growth arrest in S. cerevisiae and interacts with the anaphase-promoting complex/cyclosome. J Cell Biol 154:331–344CrossRefPubMedPubMedCentralGoogle Scholar
  177. Kowall N, Beal M (1991) Glutamate-, glutaminase-, and taurine-immunoreactive neurons develop neurofibrillary tangles in Alzheimer’s disease. Ann Neurol 29:162–167CrossRefPubMedGoogle Scholar
  178. Kraft C, Herzog F, Gieffers C, Mechtler K, Hagting A, Pines J, Peters JM (2003) Mitotic regulation of the human anaphase-promoting complex by phosphorylation. EMBO J 22:6598–6609CrossRefPubMedPubMedCentralGoogle Scholar
  179. Kramer ER, Scheuringer N, Podtelejnikov AV, Mann M, Peters JM (2000) Mitotic regulation of the APC activator proteins CDC20 and CDH1. Mol Biol Cell 11:1555–1569CrossRefPubMedPubMedCentralGoogle Scholar
  180. Kucharski T, Gamache I, Gjoerup O, Teodoro J (2011) DNA damage response signaling triggers nuclear localization of the chicken anemia virus protein apoptin. J Virol 85:12638–12649CrossRefPubMedPubMedCentralGoogle Scholar
  181. Kucharski T, Ng T, Sharon D, Navid-Azarbaijani P, Tavassoli M, Teodoro J (2016) Activation of the chicken anemia virus apoptin protein by Chk1/2 phosphorylation is required for apoptotic activity and efficient viral replication. J Virol 90:9433–9445CrossRefPubMedPubMedCentralGoogle Scholar
  182. Kuczera T, Stilling R, Hsia H, Bahari-Javan S, Irniger S, Nasmyth K, Sananbenesi F, Fischer A (2010) The anaphase promoting complex is required for memory function in mice. Learn Mem 18:49–57CrossRefPubMedGoogle Scholar
  183. Lai F, Hu K, Wu Y, Tang J, Sang Y, Cao J, Kang T (2012) Human KIAA1018/FAN1 nuclease is a new mitotic substrate of APC/C(Cdh1). Chin J Cancer 31:440–448CrossRefPubMedPubMedCentralGoogle Scholar
  184. Lara-Gonzalez P, Taylor S (2012) Cohesion fatigue explains why pharmacological inhibition of the APC/C induces a spindle checkpoint-dependent mitotic arrest. PLoS ONE 7:e49041CrossRefPubMedPubMedCentralGoogle Scholar
  185. Lara-Gonzalez P, Westhorpe FG, Taylor SS (2012) The spindle assembly checkpoint. Curr Biol 22:R966–R980CrossRefPubMedGoogle Scholar
  186. Lasorella A, Stegmuller J, Guardavaccaro D, Liu G, Carro MS, Rothschild G, de la Torre-Ubieta L, Pagano M, Bonni A, Iavarone A (2006) Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth. Nature 442:471–474CrossRefPubMedGoogle Scholar
  187. Lee YK, Choi E, Kim MA, Park PG, Park NH, Lee H (2009a) BubR1 as a prognostic marker for recurrence-free survival rates in epithelial ovarian cancers. Brit J Cancer 101:504–510CrossRefPubMedGoogle Scholar
  188. Lee J, Kim J, Barbier V, Fotedar A, Fotedar R (2009b) DNA Damage Triggers p21WAF1-dependent Emi1 down-regulation that maintains G2 arrest. Mol Biol Cell 20:1891–1902CrossRefPubMedPubMedCentralGoogle Scholar
  189. Lee SJ, Rodriguez-Bravo V, Kim H, Datta S, Foley EA (2017) The PP2AB56 phosphatase promotes the association of Cdc20 with APC/C in mitosis. J Cell Sci 130:1760–1771CrossRefPubMedPubMedCentralGoogle Scholar
  190. Lehman N, Tibshirani R, Hsu J, Natkunam Y, Harris B, West R, Masek M, Montgomery K, van de Rijn M, Jackson P (2007) Oncogenic regulators and substrates of the anaphase promoting complex/cyclosome are frequently overexpressed in malignant tumors. Am J Pathol 170:1793–1805CrossRefPubMedPubMedCentralGoogle Scholar
  191. Lehman NL, Verschuren EW, Hsu JY, Cherry AM, Jackson PK (2006) Overexpression of the anaphase promoting complex/cyclosome inhibitor Emi1 leads to tetraploidy and genomic instability of p53-deficient cells. Cell Cycle 5:1569–1573CrossRefPubMedGoogle Scholar
  192. Li GQ, Li H, Zhang HF (2003) Mad2 and p53 expression profiles in colorectal cancer and its clinical significance. World J Gastroenterol 9:1972–1975CrossRefPubMedPubMedCentralGoogle Scholar
  193. Li J, Gao J, Du J, Huang Z, Wei L (2014) Increased CDC20 expression is associated with development and progression of hepatocellular carcinoma. Int J Oncol 45:1547–1555CrossRefPubMedGoogle Scholar
  194. Li K, Mao Y, Lu L, Hu C, Wang D, Si-Tu J, Lu M, Peng S, Qiu J, Gao X (2016) Silencing of CDC20 suppresses metastatic castration-resistant prostate cancer growth and enhances chemosensitivity to docetaxel. Int J Oncol 49:1679–1685CrossRefPubMedGoogle Scholar
  195. Li M, Shin Y, Hou L, Huang X, Wei Z, Klann E, Zhang P (2008) The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memory. Nat Cell Biol 10:1083–1089CrossRefPubMedPubMedCentralGoogle Scholar
  196. Li B, Sun M, Zhang L, Takahashi S, Ma W, Vinade L, Kulkarni A, Brady R, Pant H (2001) Regulation of NMDA receptors by cyclin-dependent kinase-5. Proc Natl Acad Sci USA 98:12742–12747CrossRefPubMedGoogle Scholar
  197. Li R, Wan B, Zhou J, Wang Y, Luo T, Gu X, Chen F, Yu L (2012) APC/C(Cdh1) targets brain-specific kinase 2 (BRSK2) for degradation via the ubiquitin-proteasome pathway. PLoS ONE 7:e45932CrossRefPubMedPubMedCentralGoogle Scholar
  198. Li L, Zhou Y, Wang GF, Liao SC, Ke YB, Wu W, Li XH, Zhang RL, Fu YC (2011) Anaphase-promoting complex/cyclosome controls HEC1 stability. Cell Prolif 44:1–9CrossRefPubMedGoogle Scholar
  199. Liang M, Geisbert T, Yao Y, Hinrichs S, Giam C (2002) Human T-Lymphotropic virus type 1 oncoprotein tax promotes S-phase entry but blocks mitosis. J Virol 76:4022–4033CrossRefPubMedPubMedCentralGoogle Scholar
  200. Lim HJ, Dimova NV, Tan MK, Sigoillot FD, King RW, Shi Y (2013) The G2/M regulator histone demethylase PHF8 is targeted for degradation by the anaphase-promoting complex containing CDC20. Mol Cell Biol 33:4166–4180CrossRefPubMedPubMedCentralGoogle Scholar
  201. Lindberg J, Mills I, Klevebring D, Liu W, Neiman M, Xu J, Wikström P, Wiklund P, Wiklund F, Egevad L, Grönberg H (2013) The mitochondrial and autosomal mutation landscapes of prostate cancer. Eur Urol 63:702–708CrossRefPubMedGoogle Scholar
  202. Lindon C, Pines J (2004) Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells. J Cell Biol 164:233–241CrossRefPubMedPubMedCentralGoogle Scholar
  203. Liot C, Seguin L, Siret A, Crouin C, Schmidt S, Bertoglio J (2011) APC(cdh1) mediates degradation of the oncogenic Rho-GEF Ect2 after mitosis. PLoS ONE 6:e23676CrossRefPubMedPubMedCentralGoogle Scholar
  204. Lipkowitz S, Weissman AM (2011) RINGs of good and evil: RING finger ubiquitin ligases at the crossroads of tumour suppression and oncogenesis. Nat Rev Cancer 11:629–643CrossRefPubMedPubMedCentralGoogle Scholar
  205. Litchfield K, Summersgill B, Yost S, Sultana R, Labreche K, Dudakia D, Renwick A, Seal S, Al-Saadi R, Broderick P, Turner N, Houlston R, Huddart R, Shipley J, Turnbull C (2015) Whole-exome sequencing reveals the mutational spectrum of testicular germ cell tumours. Nat Comm 6:5973CrossRefGoogle Scholar
  206. Littlepage LE, Ruderman JV (2002) Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit. Genes Dev 16:2274–2285CrossRefPubMedPubMedCentralGoogle Scholar
  207. Liu AW, Cai J, Zhao XL, Xu AM, Fu HQ, Nian H, Zhang SH (2009) The clinicopathological significance of BUBR1 overexpression in hepatocellular carcinoma. J Clin Pathol 62:1003–1008CrossRefPubMedGoogle Scholar
  208. Liu X, Chen Y, Li Y, Petersen R, Huang K (2019) Targeting mitosis exit: a brake for cancer cell proliferation. Biochim Biophys Acta Rev Cancer 1871:179–191CrossRefPubMedGoogle Scholar
  209. Liu J, Grimison B, Maller JL (2007) New insight into metaphase arrest by cytostatic factor: from establishment to release. Oncogene 26:1286–1289CrossRefPubMedGoogle Scholar
  210. Liu B, Hong S, Tang Z, Yu H, Giam C (2004) HTLV-I Tax directly binds the Cdc20-associated anaphase-promoting complex and activates it ahead of schedule. Proc Natl Acad Sci USA 102:63–68CrossRefPubMedGoogle Scholar
  211. Liu B, Liang M, Kuo Y, Liao W, Boros I, Kleinberger T, Blancato J, Giam C (2003) Human T- Lymphotropic Virus Type 1 oncoprotein tax promotes unscheduled degradation of Pds1p/securin and Clb2p/Cyclin B1 and causes chromosomal instability. Mol Cell Biol 23:5269–5281CrossRefPubMedPubMedCentralGoogle Scholar
  212. London N, Biggins S (2014) Signalling dynamics in the spindle checkpoint response. Nat Rev Mol Cell Biol 15:736–747CrossRefPubMedPubMedCentralGoogle Scholar
  213. Los M, Panigrahi S, Rashedi I, Mandal S, Stetefeld J, Essmann F, Schulze-Osthoff K (2009) Apoptin, a tumor-selective killer. Biochim Biophys Acta Mol Cell Res 1793:1335–1342CrossRefGoogle Scholar
  214. Lu L, Hu S, Wei R, Qiu X, Lu K, Fu Y, Li H, Xing G, Li D, Peng R, He F, Zhang L (2013) The HECT type ubiquitin ligase NEDL2 is degraded by anaphase-promoting complex/cyclosome (APC/C)-Cdh1, and its tight regulation maintains the metaphase to anaphase transition. J Biol Chem 288:35637–35650CrossRefPubMedPubMedCentralGoogle Scholar
  215. Lub S, Maes A, Maes K, De Veirman K, De Bruyne E, Menu E, Fostier K, Kassambara A, Moreaux J, Hose D, Leleu X, King R, Vanderkerken K, Van Valckenborgh E (2016) Inhibiting the anaphase promoting complex/cyclosome induces a metaphase arrest and cell death in multiple myeloma cells. Oncotarget 7:4062–4076PubMedGoogle Scholar
  216. Luetjens C, Bui N, Sengpiel B, Münstermann G, Poppe M, Krohn A, Bauerbach E, Krieglstein J, Prehn J (2000) Delayed mitochondrial dysfunction in excitotoxic neuron death: cytochromecrelease and a secondary increase in superoxide production. J Neurosci 20:5715–5723CrossRefPubMedPubMedCentralGoogle Scholar
  217. Maestre C, Delgado-Esteban M, Gomez-Sanchez J, Bolaños J, Almeida A (2008) Cdk5 phosphorylates Cdh1 and modulates cyclin B1 stability in excitotoxicity. EMBO J 27:2736–2745CrossRefPubMedPubMedCentralGoogle Scholar
  218. Manchado E, Guillamot M, de Carcer G, Eguren M, Trickey M, Garcia-Higuera I, Moreno S, Yamano H, Canamero M, Malumbres M (2010) Targeting mitotic exit leads to tumor regression in vivo: modulation by Cdk1, Mastl, and the PP2A/B55alpha, delta phosphatase. Cancer Cell 18:641–654CrossRefPubMedGoogle Scholar
  219. Mao D, Gujar A, Mahlokozera T, Chen I, Pan Y, Luo J, Brost T, Thompson E, Turski A, Leuthardt E, Dunn G, Chicoine M, Rich K, Dowling J, Zipfel G, Dacey R, Achilefu S, Tran D, Yano H, Kim AA (2015) CDC20-APC/SOX2 signaling axis regulates human glioblastoma stem-like cells. Cell Rep 11:1809–1821CrossRefPubMedPubMedCentralGoogle Scholar
  220. Mao Y, Li K, Lu L, Si-tu J, Lu M, Gao X (2016) Overexpression of Cdc20 in clinically localized prostate cancer: relation to high Gleason score and biochemical recurrence after laparoscopic radical prostatectomy. Cancer Biomark 16:351–358CrossRefPubMedGoogle Scholar
  221. Maoz T, Koren R, Ben-Ari I, Kleinberger T (2005) YND1 interacts with CDC55 and is a novel mediator of E4orf4-induced toxicity. J Biol Chem 280:41270–41277CrossRefPubMedGoogle Scholar
  222. Margottin-Goguet F, Hsu JY, Loktev A, Hsieh HM, Reimann JD, Jackson PK (2003) Prophase destruction of Emi1 by the SCFβTrCP/Slimb ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Dev Cell 4:813–826Google Scholar
  223. Martin-Lluesma S, Schaeffer C, Robert E, van Breugel P, Leupin O, Hantz O, Strubin M (2008) Hepatitis B virus X protein affects S phase progression leading to chromosome segregation defects by binding to damaged DNA binding protein 1. Hepatology 48:1467–1476CrossRefPubMedGoogle Scholar
  224. Marucci G, Morandi L, Magrini E, Farnedi A, Franceschi E, Miglio R, Calo D, Pession A, Foschini MP, Eusebi V (2008) Gene expression profiling in glioblastoma and immunohistochemical evaluation of IGFBP-2 and CDC20. Virchows Arch 453:599–609CrossRefPubMedGoogle Scholar
  225. Matyskiela ME, Morgan DO (2009) Analysis of activator-binding sites on the APC/C supports a cooperative substrate-binding mechanism. Mol Cell 34:68–80CrossRefPubMedPubMedCentralGoogle Scholar
  226. McGarry TJ, Kirschner MW (1998) Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell 93:1043–1053CrossRefPubMedGoogle Scholar
  227. McLean JR, Chaix D, Ohi MD, Gould KL (2011) State of the APC/C: organization, function, and structure. Crit Rev Biochem Mol Biol 46:118–136CrossRefPubMedPubMedCentralGoogle Scholar
  228. Meghini F, Martins T, Tait X, Fujimitsu K, Yamano H, Glover D, Kimata Y (2016) Targeting of Fzr/Cdh1 for timely activation of the APC/C at the centrosome during mitotic exit. Nat Comm 7:12607CrossRefGoogle Scholar
  229. Menyhárt O, Nagy Á, Győrffy B (2018) Determining consistent prognostic biomarkers of overall survival and vascular invasion in hepatocellular carcinoma. R Soc Open Sci 5:181006CrossRefPubMedPubMedCentralGoogle Scholar
  230. Metzger MB, Hristova VA, Weissman AM (2012) HECT and RING finger families of E3 ubiquitin ligases at a glance. J Cell Sci 125:531–537CrossRefPubMedPubMedCentralGoogle Scholar
  231. Meyer SK, Dunn M, Vidler DS, Porter A, Blain PG, Jowsey PA (2019) Phosphorylation of MCPH1 isoforms during mitosis followed by isoform-specific degradation by APC/C-CDH1. FASEB J 33:2796–2808CrossRefPubMedGoogle Scholar
  232. Michaelis C, Ciosk R, Nasmyth K (1997) Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91:35–45CrossRefPubMedGoogle Scholar
  233. Miller JJ, Summers MK, Hansen DV, Nachury MV, Lehman NL, Loktev A, Jackson PK (2006) Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor. Genes Dev 20:2410–2420CrossRefPubMedPubMedCentralGoogle Scholar
  234. Miron M, Blanchette P, Groitl P, Dallaire F, Teodoro J, Li S, Dobner T, Branton P (2008) Localization and importance of the adenovirus E4orf4 protein during lytic infection. J Virol 83:1689–1699CrossRefPubMedPubMedCentralGoogle Scholar
  235. Mo M, Fleming S, Mercer A (2009) Cell cycle deregulation by a poxvirus partial mimic of anaphase-promoting complex subunit 11. Proc Natl Acad Sci USA 106:19527–19532CrossRefPubMedGoogle Scholar
  236. Mo M, Fleming S, Mercer A (2010a) Changing pace: viral mimicry of an anaphase promoting complex subunit. Cell Cycle 9:632–633CrossRefPubMedGoogle Scholar
  237. Mo M, Fleming S, Mercer A (2010b) Orf virus cell cycle regulator, PACR, competes with subunit 11 of the anaphase promoting complex for incorporation into the complex. J Gen Virol 91:3010–3015CrossRefPubMedGoogle Scholar
  238. Mo M, Shahar S, Fleming S, Mercer A (2012) How viruses affect the cell cycle through manipulation of the APC/C. Trends Microbiol 20:440–448CrossRefPubMedGoogle Scholar
  239. Mondal G, Sengupta S, Panda CK, Gollin SM, Saunders WS, Roychoudhury S (2007) Overexpression of Cdc20 leads to impairment of the spindle assembly checkpoint and aneuploidization in oral cancer. Carcinogenesis 28:81–92CrossRefPubMedGoogle Scholar
  240. Montero A, Fossella F, Hortobagyi G, Valero V (2005) Docetaxel for treatment of solid tumours: a systematic review of clinical data. Lancet Oncol 6:229–239CrossRefPubMedGoogle Scholar
  241. Morrow CJ, Tighe A, Johnson VL, Scott MI, Ditchfield C, Taylor SS (2005) Bub1 and aurora B cooperate to maintain BubR1-mediated inhibition of APC/CCdc20. J Cell Sci 118:3639–3652CrossRefPubMedGoogle Scholar
  242. Mosch B, Morawski M, Mittag A, Lenz D, Tarnok A, Arendt T (2007) Aneuploidy and DNA replication in the normal human brain and alzheimer’s disease. J Neurosci 27:6859–6867CrossRefPubMedPubMedCentralGoogle Scholar
  243. Moura IM, Delgado ML, Silva PM, Lopes CA, do Amaral JB, Monteiro LS, Bousbaa H (2014) High CDC20 expression is associated with poor prognosis in oral squamous cell carcinoma. J Oral Pathol Med 43:225–231Google Scholar
  244. Mu Y, Gage F (2011) Adult hippocampal neurogenesis and its role in Alzheimer’s disease. Mol Neurodegener 6:85CrossRefPubMedPubMedCentralGoogle Scholar
  245. Mui M, Roopchand D, Gentry M, Hallberg R, Vogel J, Branton P (2010) Adenovirus protein E4orf4 induces premature APCCdc20 activation in Saccharomyces cerevisiae by a protein phosphatase 2A-dependent mechanism. J Virol 84:4798–4809CrossRefPubMedPubMedCentralGoogle Scholar
  246. Musacchio A (2011) Spindle assembly checkpoint: the third decade, philosophical transactions of the royal society of London. Series B Biol Sci 366:3595–3604CrossRefGoogle Scholar
  247. Musacchio A, Salmon ED (2007) The spindle-assembly checkpoint in space and time. Nat Rev Mol Cell Biol 8:379–393CrossRefPubMedGoogle Scholar
  248. Nagy V, Dikic I (2010) Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity. Biol Chem 391:163–169CrossRefPubMedGoogle Scholar
  249. Nakayama KI, Nakayama K (2006) Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer 6:369–381CrossRefPubMedGoogle Scholar
  250. Nalepa G, Rolfe M, Harper JW (2006) Drug discovery in the ubiquitin-proteasome system. Nat Rev Drug Discov 5:596–613CrossRefPubMedPubMedCentralGoogle Scholar
  251. Naoe H, Araki K, Nagano O, Kobayashi Y, Ishizawa J, Chiyoda T, Shimizu T, Yamamura K, Sasaki Y, Saya H, Kuninaka S (2010) The anaphase-promoting complex/cyclosome activator Cdh1 modulates Rho GTPase by targeting p190 RhoGAP for degradation. Mol Cell Biol 30:3994–4005CrossRefPubMedPubMedCentralGoogle Scholar
  252. Nguyen D, Alavi M, Kim K, Kang T, Scott R, Noh Y, Lindsey J, Wissinger B, Ellisman M, Weinreb R, Perkins G, Ju W (2011) A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics. Cell Death Dis 2:e240CrossRefPubMedPubMedCentralGoogle Scholar
  253. Nguyen HG, Chinnappan D, Urano T, Ravid K (2005) Mechanism of Aurora-B degradation and its dependency on intact KEN and A-boxes: identification of an aneuploidy-promoting property. Mol Cell Biol 25:4977–4992CrossRefPubMedPubMedCentralGoogle Scholar
  254. Nishimura K, Oki T, Kitaura J, Kuninaka S, Saya H, Sakaue-Sawano A, Miyawaki A, Kitamura T (2013) APC(CDH1) targets MgcRacGAP for destruction in the late M phase. PLoS ONE 8:e63001CrossRefPubMedPubMedCentralGoogle Scholar
  255. Noteborn M (2004) Chicken anemia virus induced apoptosis: underlying molecular mechanisms. Vet Microbiol 98:89–94CrossRefPubMedPubMedCentralGoogle Scholar
  256. Noteborn M (2009) Proteins selectively killing tumor cells. Eur J Pharmacol 625:165–173CrossRefPubMedPubMedCentralGoogle Scholar
  257. Ohoka N, Sakai S, Onozaki K, Nakanishi M, Hayashi H (2010) Anaphase-promoting complex/cyclosome-cdh1 mediates the ubiquitination and degradation of TRB3. Biochem Biophys Res Commun 392:289–294CrossRefPubMedPubMedCentralGoogle Scholar
  258. Ostapenko D, Solomon MJ (2011) Anaphase promoting complex-dependent degradation of transcriptional repressors Nrm1 and Yhp1 in Saccharomyces cerevisiae. Mol Biol Cell 22:2175–2184Google Scholar
  259. Pandey V, Kumar V (2012) HBx protein of hepatitis B virus promotes reinitiation of DNA replication by regulating expression and intracellular stability of replication licensing factor CDC6. J Biol Chem 287:20545–20554CrossRefPubMedPubMedCentralGoogle Scholar
  260. Park K, Choi S, Eom M, Kang Y (2005) Downregulation of the anaphase-promoting complex (APC)7 in invasive ductal carcinomas of the breast and its clinicopathologic relationships. Breast Cancer Res 7:R238–R247CrossRefPubMedPubMedCentralGoogle Scholar
  261. Park HJ, Costa RH, Lau LF, Tyner AL, Raychaudhuri P (2008) Anaphase-promoting complex/cyclosome-CDH1-mediated proteolysis of the forkhead box M1 transcription factor is critical for regulated entry into S phase. Mol Cell Biol 28:5162–5171CrossRefPubMedPubMedCentralGoogle Scholar
  262. Parmar MB, KC RB, Löbenberg R, Uludağ H (2018) Additive polyplexes to undertake siRNA therapy against CDC20 and survivin in breast cancer cells. Biomacromolecules 19:4193–4206Google Scholar
  263. Parmar M, Meenakshi Sundaram D, KC R, Maranchuk R, Montazeri Aliabadi H, Hugh J, Löbenberg R, Uludağ H (2018) Combinational siRNA delivery using hyaluronic acid modified amphiphilic polyplexes against cell cycle and phosphatase proteins to inhibit growth and migration of triple-negative breast cancer cells. Acta Biomater 66:294–309Google Scholar
  264. Passmore LA, Booth CR, Vénien-Bryan C, Ludtke SJ, Fioretto C, Johnson LN, Chiu W, Barford D (2005) Structural analysis of the anaphase-promoting complex reveals multiple active sites and insights into polyubiquitylation. Mol Cell 20:855–866CrossRefGoogle Scholar
  265. Patel D, McCance D (2010) Compromised spindle assembly checkpoint due to altered expression of Ubch10 and Cdc20 in human papillomavirus Type 16 E6- and E7-expressing keratinocytes. J Virol 84:10956–10964CrossRefPubMedPubMedCentralGoogle Scholar
  266. Penas C, Govek E, Fang Y, Ramachandran V, Daniel M, Wang W, Maloof M, Rahaim R, Bibian M, Kawauchi D, Finkelstein D, Han J, Long J, Li B, Robbins D, Malumbres M, Roussel M, Roush W, Hatten M, Ayad N (2015) Casein kinase 1δ Is an APC/CCdh1 substrate that regulates cerebellar granule cell neurogenesis. Cell Rep 11:249–260CrossRefPubMedPubMedCentralGoogle Scholar
  267. Penrose K, McBride A (2000) Proteasome-mediated degradation of the papillomavirus E2-TA protein is regulated by phosphorylation and can modulate viral genome copy number. J Virol 74:6031–6038CrossRefPubMedPubMedCentralGoogle Scholar
  268. Peters JM (2006) The anaphase promoting complex/cyclosome: a machine designed to destroy. Nature Rev Mol Cell Biol 7:644–656CrossRefGoogle Scholar
  269. Petersen B, Wagener C, Marinon F, Kramer E, Melixetian M, Denchi E, Gieffers C, Matteucci C, Peters J, Helin K (2000) Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1. Genes Dev 14:2330–2343CrossRefPubMedPubMedCentralGoogle Scholar
  270. Petroski MD, Deshaies RJ (2005) Function and regulation of cullin-RING ubiquitin ligases. Nature Rev Mol Cell Biol 6:9–20CrossRefGoogle Scholar
  271. Pfleger CM, Kirschner MW (2000) The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. Genes Dev 14:655–665PubMedPubMedCentralGoogle Scholar
  272. Pick J, Malumbres M, Klann E (2012) The E3 ligase APC/C-Cdh1 is required for associative fear memory and long-term potentiation in the amygdala of adult mice. Learn Mem 20:11–20CrossRefPubMedPubMedCentralGoogle Scholar
  273. Pickart CM (2001) Mechanisms underlying ubiquitination. Ann Rev Biochem 70:503–533CrossRefPubMedPubMedCentralGoogle Scholar
  274. Pines J (2011) Cubism and the cell cycle: the many faces of the APC/C. Nat Rev Mol Cell Biol 12:427–438CrossRefPubMedPubMedCentralGoogle Scholar
  275. Ping Z, Lim R, Bashir T, Pagano M, Guardavaccaro D (2012) APC/C (Cdh1) controls the proteasome-mediated degradation of E2F3 during cell cycle exit. Cell Cycle 11:1999–2005CrossRefPubMedPubMedCentralGoogle Scholar
  276. Pinto M, Vieira J, Ribeiro FR, Soares MJ, Henrique R, Oliveira J, Jerónimo Teixeira MR (2008) Overexpression of the mitotic checkpoint genes BUB1 and BUBR1 is associated with genomic complexity in clear cell kidney carcinomas. Cell Oncol 30:389–395PubMedPubMedCentralGoogle Scholar
  277. Powers C, DeFilippis V, Malouli D, Fruh K (2008) Cytomegalovirus immune evasion. Curr Top Microbiol Immunol 325:333–359PubMedPubMedCentralGoogle Scholar
  278. Prasetyo A, Kamahora T, Kuroishi A, Murakami K, Hino S (2009) Replication of chicken anemia virus (CAV) requires apoptin and is complemented by VP3 of human torque teno virus (TTV). Virol 385:85–92CrossRefGoogle Scholar
  279. Puram SV, Bonni A (2011) Novel functions for the anaphase-promoting complex in neurobiology. Semin Cell Dev Biol 22:586–594CrossRefPubMedPubMedCentralGoogle Scholar
  280. Qi W, Yu H (2007) KEN-box-dependent degradation of the Bub1 spindle checkpoint kinase by the anaphase-promoting complex/cyclosome. J Biol Chem 282:3672–3679CrossRefPubMedPubMedCentralGoogle Scholar
  281. Qian Z, Leung-Pineda V, Xuan B, Piwnica-Worms H, Yu D (2010) Human cytomegalovirus protein pUL117 targets the mini-chromosome maintenance complex and suppresses cellular DNA synthesis. PLoS Pathog 6:e1000814CrossRefPubMedPubMedCentralGoogle Scholar
  282. Qiu L, Tan X, Lin J, Liu R, Chen S, Geng R, Wu J, Huang W (2017) CDC27 induces metastasis and invasion in colorectal cancer via the promotion of epithelial-to-mesenchymal transition. J Cancer 8:2626–2635CrossRefPubMedPubMedCentralGoogle Scholar
  283. Qiu L, Wu J, Pan C, Tan X, Lin J, Liu R, Chen S, Geng R, Huang W (2016) Downregulation of CDC27 inhibits the proliferation of colorectal cancer cells via the accumulation of p21Cip1/Waf1. Cell Death Dis 7:e2074CrossRefPubMedPubMedCentralGoogle Scholar
  284. Rahimi H, Ahmadzadeh A, Yousef-amoli S, Kokabee L, Shokrgozar M, Mahdian R, Karimipoor M (2015) The expression pattern of APC2 and APC7 in various cancer cell lines and AML patients. Adv Med Sci 60:259–263CrossRefPubMedPubMedCentralGoogle Scholar
  285. Ramanujan A, Tiwari S (2016) APC/C and retinoblastoma interaction: cross-talk of retinoblastoma protein with the ubiquitin proteasome pathway. Biosci Rep 36:e00377CrossRefPubMedPubMedCentralGoogle Scholar
  286. Ranganathan P, Clark P, Kuo J, Salamat M, Kalejta R (2011) Significant association of multiple human cytomegalovirus genomic loci with glioblastoma multiforme samples. J Virol 86:854–864CrossRefPubMedPubMedCentralGoogle Scholar
  287. Rape M (2010) Assembly of k11-linked ubiquitin chains by the anaphase-promoting complex. Subcell Biochem 54:107–115CrossRefPubMedPubMedCentralGoogle Scholar
  288. Rape M, Kirschner MW (2004) Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry. Nature 432:588–595CrossRefPubMedPubMedCentralGoogle Scholar
  289. Reimann JD, Freed E, Hsu JY, Kramer ER, Peters JM, Jackson PK (2001) Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell 105:645–655CrossRefPubMedPubMedCentralGoogle Scholar
  290. Reimann E, Kõks S, Ho X, Maasalu K, Märtson A (2014) Whole exome sequencing of a single osteosarcoma case¿integrative analysis with whole transcriptome RNA-seq data. Hum Genomics 8:20PubMedPubMedCentralGoogle Scholar
  291. Rimkus C, Friederichs J, Rosenberg R, Holzmann B, Siewert JR, Janssen KP (2007) Expression of the mitotic checkpoint gene MAD2L2 has prognostic significance in colon cancer. Int J Cancer 120:207–211CrossRefPubMedPubMedCentralGoogle Scholar
  292. Rodriguez-Rodriguez P, Almeida A, Bolaños J (2013) Brain energy metabolism in glutamate-receptor activation and excitotoxicity: Role for APC/C-Cdh1 in the balance glycolysis/pentose phosphate pathway. Neurochem Int 62:750–756CrossRefPubMedGoogle Scholar
  293. Rotin D, Kumar S (2009) Physiological functions of the HECT family of ubiquitin ligases. Nature Rev Mol Cell Biol 10:398–409CrossRefGoogle Scholar
  294. Sackton K, Dimova N, Zeng X, Tian W, Zhang M, Sackton T, Meaders J, Pfaff K, Sigoillot F, Yu H, Luo X, King R (2014) Synergistic blockade of mitotic exit by two chemical inhibitors of the APC/C. Nature 514:646–649CrossRefPubMedPubMedCentralGoogle Scholar
  295. Sacristan C, Kops GJ (2015) Joined at the hip: kinetochores, microtubules, and spindle assembly checkpoint signaling. Trends Cell Biol 25:21–28CrossRefPubMedGoogle Scholar
  296. Sandhu SK, Kaur G (2002) Alterations in oxidative stress scavenger system in aging rat brain and lymphocytes. Biogerontology 3:161–173CrossRefPubMedGoogle Scholar
  297. Sansregret L, Patterson J, Dewhurst S, López-García C, Koch A, McGranahan N, Chao W, Barry D, Rowan A, Instrell R, Horswell S, Way M, Howell M, Singleton M, Medema R, Nurse P, Petronczki M, Swanton C (2017) APC/C dysfunction limits excessive cancer chromosomal instability. Cancer Discov 7:218–233CrossRefPubMedPubMedCentralGoogle Scholar
  298. Sasaki T, Senda M, Kim SN, Kojima S, Kubodera A (2001) Age-related changes of glutathione content, glucose transport and metabolism, and mitochondrial electron transfer function in mouse brain. Nucl Med Biol 28:25–31CrossRefPubMedGoogle Scholar
  299. Saxena N, Kumar V (2014) The HBx oncoprotein of hepatitis B virus deregulates the cell cycle by promoting the intracellular accumulation and re-compartmentalization of the cellular deubiquitinase USP37. PLoS ONE 9:e111256CrossRefPubMedPubMedCentralGoogle Scholar
  300. Schreiber A, Stengel F, Zhang Z, Enchev RI, Kong EH, Morris EP, Robinson CV, da Fonseca PC, Barford D (2011) Structural basis for the subunit assembly of the anaphase-promoting complex. Nature 470:227–232CrossRefPubMedGoogle Scholar
  301. Schuyler S, Wu Y, Chen H, Ding Y, Lin C, Chu Y, Chen T, Liao L, Tsai W, Huang A, Wang L, Liao T, Jhuo J, Cheng V (2018) Peptide inhibitors of the anaphase promoting-complex that cause sensitivity to microtubule poison. PLoS ONE 13:e0198930CrossRefPubMedPubMedCentralGoogle Scholar
  302. Schwab M, Neutzner M, Möcker D, Seufert W (2001) Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC. EMBO J 20:5165–5175CrossRefPubMedPubMedCentralGoogle Scholar
  303. Sedgwick GG, Hayward DG, Di Fiore B, Pardo M, Yu L, Pines J, Nilsson J (2013) Mechanisms controlling the temporal degradation of Nek2A and Kif18A by the APC/C-Cdc20 complex. EMBO J 32:303–314CrossRefPubMedPubMedCentralGoogle Scholar
  304. Seike M, Gemma A, Hosoya Y, Hosomi Y, Okano T, Kurimoto F, Uematsu K, Takenaka K, Yoshimura A, Shibuya M, Ui-Tei K, Kudoh S (2002) The promoter region of the human BUBR1 gene and its expression analysis in lung cancer. Lung Cancer 38:229–234CrossRefPubMedGoogle Scholar
  305. Seki A, Fang G (2007) CKAP2 is a spindle-associated protein degraded by APC/C-Cdh1 during mitotic exit. J Biol Chem 282:15103–15113CrossRefPubMedGoogle Scholar
  306. Shi R, Sun Q, Sun J, Wang X, Xia W, Dong G, Wang A, Jiang F, Xu L (2017) Cell division cycle 20 overexpression predicts poor prognosis for patients with lung adenocarcinoma. Tumor Biol 39:101042831769223CrossRefGoogle Scholar
  307. Shimizu N, Nakajima N, Tsunematsu T, Ogawa I, Kawai H, Hirayama R, Fujimori A, Yamada A, Okayasu R, Ishimaru N, Takata T, Kudo Y (2013) Selective enhancing effect of early mitotic inhibitor 1 (Emi1) depletion on the sensitivity of doxorubicin or X-ray treatment in human cancer cells. J Biol Chem 288:17238–17252CrossRefPubMedPubMedCentralGoogle Scholar
  308. Simpson-Lavy KJ, Sajman J, Zenvirth D, Brandeis M (2009) APC/CCdh1 specific degradation of Hsl1 and Clb2 is required for proper stress responses of S. cerevisiae. Cell Cycle 8:3003–3009CrossRefPubMedGoogle Scholar
  309. Sivakumar S, Gorbsky GJ (2015) Spatiotemporal regulation of the anaphase-promoting complex in mitosis. Nat Rev Mol Cell Biol 16:82–94CrossRefPubMedPubMedCentralGoogle Scholar
  310. Skaar JR, Pagano M (2009) Control of cell growth by the SCF and APC/C ubiquitin ligases. Curr Opin Cell Biol 21:816–824CrossRefPubMedPubMedCentralGoogle Scholar
  311. Song L, Rape M (2010) Regulated degradation of spindle assembly factors by the anaphase-promoting complex. Mol Cell 38:369–382CrossRefPubMedPubMedCentralGoogle Scholar
  312. Soroceanu L, Cobbs C (2011) Is HCMV a tumor promoter? Virus Res 157:193–203CrossRefPubMedGoogle Scholar
  313. Sotillo R, Hernando E, Diaz-Rodriguez E, Teruya-Feldstein J, Cordon-Cardo C, Lowe SW, Benezra R (2007) Mad2 overexpression promotes aneuploidy and tumorigenesis in mice. Cancer Cell 11:9–23CrossRefPubMedGoogle Scholar
  314. Stegmuller J, Konishi Y, Huynh MA, Yuan Z, Dibacco S, Bonni A (2006) Cell-intrinsic regulation of axonal morphogenesis by the Cdh1-APC target SnoN. Neuron 50:389–400CrossRefPubMedGoogle Scholar
  315. Stevens D, Gassmann R, Oegema K, Desai A (2011) Uncoordinated loss of chromatid cohesion is a common outcome of extended metaphase arrest. PLoS ONE 6:e22969CrossRefPubMedPubMedCentralGoogle Scholar
  316. Stewart S, Fang G (2005) Destruction box-dependent degradation of aurora B is mediated by the anaphase-promoting complex/cyclosome and Cdh1. Cancer Res 65:8730–8735CrossRefPubMedGoogle Scholar
  317. Sugimoto N, Kitabayashi I, Osano S, Tatsumi Y, Yugawa T, Narisawa-Saito M, Matsukage A, Kiyono T, Fujita M (2008) Identification of novel human Cdt1-binding proteins by a proteomics approach: proteolytic regulation by APC/CCdh1. Mol Biol Cell 19:1007–1021CrossRefPubMedPubMedCentralGoogle Scholar
  318. Sun J, Karoulia Z, Wong EY, Ahmed M, Itoh K, Xu PX (2013) The phosphatase-transcription activator EYA1 is targeted by anaphase-promoting complex/Cdh1 for degradation at M-to-G1 transition. Mol Cell Biol 33:927–936CrossRefPubMedPubMedCentralGoogle Scholar
  319. Takahashi A, Imai Y, Yamakoshi K, Kuninaka S, Ohtani N, Yoshimoto S, Hori S, Tachibana M, Anderton E, Takeuchi T, Shinkai Y, Peters G, Saya H, Hara E (2012) DNA damage signaling triggers degradation of histone methyltransferases through APC/C(Cdh1) in senescent cells. Mol Cell 45:123–131CrossRefPubMedGoogle Scholar
  320. Tan C, Teissier S, Gunaratne J, Quek L, Bellanger S (2015) Stranglehold on the spindle assembly checkpoint: the human papillomavirus E2 protein provokes BUBR1-dependent aneuploidy. Cell Cycle 14:1459–1470CrossRefPubMedPubMedCentralGoogle Scholar
  321. Tanaka K, Nishioka J, Kato K, Nakamura A, Mouri T, Miki C, Kusunoki M, Nobori T (2001) Mitotic checkpoint protein hsMAD2 as a marker predicting liver metastasis of human gastric cancers. Jpn J Cancer Res 92:952–958CrossRefPubMedPubMedCentralGoogle Scholar
  322. Tang Z, Shu H, Oncel D, Chen S, Yu H (2004) Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint. Mol Cell 16:387–397CrossRefPubMedGoogle Scholar
  323. Taniguchi K, Momiyama N, Ueda M, Matsuyama R, Mori R, Fujii Y, Ichikawa Y, Endo I, Togo S, Shimada H (2008) Targeting of CDC20 via small interfering RNA causes enhancement of the cytotoxicity of chemoradiation. Anticancer Res 28:1559–1563PubMedGoogle Scholar
  324. Teng FY, Tang BL (2005) APC/C regulation of axonal growth and synaptic functions in postmitotic neurons: the Liprin-alpha connection. Cell Molecular Life Sci 62:1571–1578CrossRefGoogle Scholar
  325. Teodoro J, Heilman D, Parker A, Green M (2004) The viral protein Apoptin associates with the anaphase-promoting complex to induce G2/M arrest and apoptosis in the absence of p53. Genes Dev 18:1952–1957CrossRefPubMedPubMedCentralGoogle Scholar
  326. Thornton BR, Ng TM, Matyskiela ME, Carroll CW, Morgan DO, Toczyski DP (2006) An architectural map of the anaphase-promoting complex. Genes Dev 20:449–460CrossRefPubMedPubMedCentralGoogle Scholar
  327. Tipton AR, Ji W, Sturt-Gillespie B, Bekier ME 2nd, Wang K, Taylor WR, Liu ST (2013) Monopolar spindle 1 (MPS1) kinase promotes production of closed MAD2 (C-MAD2) conformer and assembly of the mitotic checkpoint complex. J Biol Chem 288:35149–35158CrossRefPubMedPubMedCentralGoogle Scholar
  328. Touati SA, Kataria M, Jones AW, Snijders AP, Uhlmann F (2018) Phosphoproteome dynamics during mitotic exit in budding yeast. EMBO J 37:pii:e98745Google Scholar
  329. Tran K, Kamil J, Coen D, Spector D (2010) Inactivation and disassembly of the anaphase-promoting complex during human cytomegalovirus infection is associated with degradation of the APC5 and APC4 subunits and does not require UL97-mediated phosphorylation of Cdh1. J Virol 84:10832–10843CrossRefPubMedPubMedCentralGoogle Scholar
  330. Tran K, Mahr J, Choi J, Teodoro J, Green M, Spector D (2007) Accumulation of substrates of the anaphase-promoting complex (APC) during human cytomegalovirus infection is associated with the phosphorylation of Cdh1 and the dissociation and relocalization of APC subunits. J Virol 82:529–537CrossRefPubMedPubMedCentralGoogle Scholar
  331. Tsai C, Nussinov R (2013) The molecular basis of targeting protein kinases in cancer therapeutics. Semin Cancer Biol 23:235–242CrossRefPubMedPubMedCentralGoogle Scholar
  332. Tu S, Okamoto S, Lipton S, Xu H (2014) Oligomeric Aβ-induced synaptic dysfunction in Alzheimer’s disease. Mol Neurodegener 9:48CrossRefPubMedPubMedCentralGoogle Scholar
  333. Tung JJ, Padmanabhan K, Hansen DV, Richter JD, Jackson PK (2007) Translational unmasking of Emi2 directs cytostatic factor arrest in meiosis II. Cell Cycle 6:725–731CrossRefPubMedGoogle Scholar
  334. Turnell A, Mymryk J (2006) Roles for the coactivators CBP and p300 and the APC/C E3 ubiquitin ligase in E1A-dependent cell transformation. Brit J Cancer 95:555–560CrossRefPubMedGoogle Scholar
  335. Turnell A, Stewart G, Grand R, Rookes S, Martin A, Yamano H, Elledge S, Gallimore P (2005) The APC/C and CBP/p300 cooperate to regulate transcription and cell-cycle progression. Nature 438:690–695CrossRefPubMedGoogle Scholar
  336. Uhlmann F, Lottspeich F, Nasmyth K (1999) Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1. Nature 400:37–42CrossRefPubMedGoogle Scholar
  337. Vanoosthuyse V, Meadows J, van der Sar S, Millar J, Hardwick K (2009) Bub3p facilitates spindle checkpoint silencing in fission yeast. Mol Biol Cell 20:5096–5105CrossRefPubMedPubMedCentralGoogle Scholar
  338. van Roessel P, Elliott DA, Robinson IM, Prokop A, Brand AH (2004) Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell 119:707–718CrossRefPubMedGoogle Scholar
  339. van’t Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415:530–536Google Scholar
  340. Veas-Pérez de Tudela M, Maestre C, Delgado-Esteban M, Bolaños J, Almeida A (2015) Cdk5-mediated inhibition of APC/C-Cdh1 switches on the cyclin D1-Cdk4-pRb pathway causing aberrant S-phase entry of postmitotic neurons. Sci Rep 5:18180CrossRefPubMedPubMedCentralGoogle Scholar
  341. Visintin R, Prinz S, Amon A (1997) CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science 278:460–463CrossRefPubMedGoogle Scholar
  342. Visintin C, Tomson BN, Rahal R, Paulson J, Cohen M, Taunton J, Amon A, Visintin R (2008) APC/C-Cdh1-mediated degradation of the Polo kinase Cdc5 promotes the return of Cdc14 into the nucleolus. Genes Dev 22:79–90CrossRefPubMedPubMedCentralGoogle Scholar
  343. Vodermaier HC, Gieffers C, Maurer-Stroh S, Eisenhaber F, Peters JM (2003) TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1. Curr Biol 13:1459–1468CrossRefPubMedGoogle Scholar
  344. Vomaske J, Varnum S, Melnychuk R, Smith P, Pasa-Tolic L, Shutthanandan J, Streblow D (2010) HCMV pUS28 initiates pro-migratory signaling via activation of Pyk2 kinase. Herpesviridae 1:2CrossRefPubMedPubMedCentralGoogle Scholar
  345. Wamelink M, Struys E, Jakobs C (2008) The biochemistry, metabolism and inherited defects of the pentose phosphate pathway: a review. J Inherit Metab Dis 31:703–717CrossRefPubMedGoogle Scholar
  346. Wan L, Tan M, Yang J, Inuzuka H, Dai X, Wu T, Liu J, Shaik S, Chen G, Deng J, Malumbres M, Letai A, Kirschner M, Sun Y, Wei W (2014) APCCdc20 suppresses apoptosis through targeting bim for ubiquitination and destruction. Dev Cell 29:377–391CrossRefPubMedPubMedCentralGoogle Scholar
  347. Wang S, Chen B, Zhu Z, Zhang L, Zeng J, Xu G, Liu G, Xiong D, Luo Q, Huang Z (2018) CDC20 overexpression leads to poor prognosis in solid tumors. Medicine 97:e13832CrossRefPubMedPubMedCentralGoogle Scholar
  348. Wang CX, Fisk BC, Wadehra M, Su H, Braun J (2000) Overexpression of murine fizzy-related (fzr) increases natural killer cell-mediated cell death and suppresses tumor growth. Blood 96:259–263CrossRefPubMedGoogle Scholar
  349. Wang R, Li KM, Zhou CH, Xue JL, Ji CN, Chen JZ (2011) Cdc20 mediates D-box-dependent degradation of Sp100. Biochem Biophys Res Commun 415:702–706CrossRefPubMedGoogle Scholar
  350. Wang Q, Moyret-Lalle C, Couzon F, Surbiguet-Clippe C, Saurin J, Lorca T, Navarro C, Puisieux A (2003) Alterations of anaphase-promoting complex genes in human colon cancer cells. Oncogene 22:1486–1490CrossRefPubMedGoogle Scholar
  351. Wang L, Yin F, Du Y, Du W, Chen B, Zhang Y, Wu K, Ding J, Liu J, Fan D (2009) MAD2 as a key component of mitotic checkpoint: a probable prognostic factor for gastric cancer. Am J Clin Pathol 131:793–801CrossRefPubMedGoogle Scholar
  352. Wang Y, Zhan Q (2007) Cell cycle-dependent expression of centrosomal ninein-like protein in human cells is regulated by the anaphase-promoting complex. J Biol Chem 282:17712–17719CrossRefPubMedGoogle Scholar
  353. Wang L, Zhang J, Wan L, Zhou X, Wang Z, Wei W (2015) Targeting Cdc20 as a novel cancer therapeutic strategy. Pharmacol Thera 151:141–151CrossRefGoogle Scholar
  354. Wasch R, Robbins JA, Cross FR (2010) The emerging role of APC/CCdh1 in controlling differentiation, genomic stability and tumor suppression. Oncogene 29:1–10CrossRefPubMedGoogle Scholar
  355. Wei W, Ayad NG, Wan Y, Zhang GJ, Kirschner MW, Kaelin WG Jr (2004) Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature 428:194–198CrossRefPubMedGoogle Scholar
  356. Whyte P, Buchkovich K, Horowitz J, Friend S, Raybuck M, Weinberg R, Harlow E (1988) Association between an oncogene and an anti-oncogene: the adenovirus E1A proteins bind to the retinoblastoma gene product. Nature 334:124–129CrossRefPubMedGoogle Scholar
  357. Wickliffe KE, Williamson A, Meyer HJ, Kelly A, Rape M (2011) K11-linked ubiquitin chains as novel regulators of cell division. Trends Cell Biol 21:656–663CrossRefPubMedPubMedCentralGoogle Scholar
  358. Wiebusch L, Bach M, Uecker R, Hagemeier C (2005) Human cytomegalovirus inactivates the G0/G1-APC/C ubiquitin ligase by Cdh1 dissociation. Cell Cycle 4:1435–1439CrossRefPubMedGoogle Scholar
  359. Wiebusch L, Hagemeier C (2010) p53- and p21-dependent premature APC/C–Cdh1 activation in G2 is part of the long-term response to genotoxic stress. Oncogene 29:3477–3489CrossRefPubMedGoogle Scholar
  360. Williams SJ, Abrieu A, Losada A (2017) Bub1 targeting to centromeres is sufficient for Sgo1 recruitment in the absence of kinetochores. Chromosoma 126:279–286CrossRefPubMedGoogle Scholar
  361. Wolthuis R, Clay-Farrace L, van Zon W, Yekezare M, Koop L, Ogink J, Medema R, Pines J (2008) Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A. Mol Cell 30:290–302CrossRefPubMedGoogle Scholar
  362. Woodbury EL, Morgan DO (2007) Cdk and APC activities limit the spindle-stabilizing function of Fin1 to anaphase. Nat Cell Biol 9:106–112CrossRefPubMedGoogle Scholar
  363. Wu F, Dai X, Gan W, Wan L, Li M, Mitsiades N, Wei W, Ding Q, Zhang J (2017) Prostate cancer-associated mutation in SPOP impairs its ability to target Cdc20 for poly-ubiquitination and degradation. Cancer Lett 385:207–214CrossRefPubMedGoogle Scholar
  364. Wu WJ, Hu KS, Wang DS, Zeng ZL, Zhang DS, Chen DL, Bai L, Xu RH (2013) CDC20 overexpression predicts a poor prognosis for patients with colorectal cancer. J Transl Med 11:142CrossRefPubMedPubMedCentralGoogle Scholar
  365. Wu F, Lin Y, Cui P, Li H, Zhang L, Sun Z, Huang S, Li S, Huang S, Zhao Q, Liu Q (2018) Cdc20/p55 mediates the resistance to docetaxel in castration-resistant prostate cancer in a Bim-dependent manner. Cancer Chemother Pharmacol 81:999–1006CrossRefPubMedGoogle Scholar
  366. Wu S, Wang W, Kong X, Congdon LM, Yokomori K, Kirschner MW, Rice JC (2010) Dynamic regulation of the PR-Set7 histone methyltransferase is required for normal cell cycle progression. Genes Dev 24:2531–2542CrossRefPubMedPubMedCentralGoogle Scholar
  367. Xie C, Powell C, Yao M, Wu J, Dong Q (2014) Ubiquitin-conjugating enzyme E2C: a potential cancer biomarker. Int J Biochem Cell Biol 47:113–117CrossRefPubMedGoogle Scholar
  368. Xin Y, Ning S, Zhang L, Cui M (2018) CDC27 facilitates gastric cancer cell proliferation, invasion and metastasis via twist-induced epithelial-mesenchymal transition. Cellular Physiol Biochem 50:501–511CrossRefGoogle Scholar
  369. Yamada M, Watanabe K, Mistrik M, Vesela E, Protivankova I, Mailand N, Lee M, Masai H, Lukas J, Bartek J (2013) ATR-Chk1-APC/CCdh1-dependent stabilization of Cdc7-ASK (Dbf4) kinase is required for DNA lesion bypass under replication stress. Genes Dev 27:2459–2472CrossRefPubMedPubMedCentralGoogle Scholar
  370. Yamaguchi M, VanderLinden R, Weissmann F, Qiao R, Dube P, Brown NG, Haselbach D, Zhang W, Sidhu SS, Peters JM, Stark H, Schulman BA (2016) Cryo-EM of mitotic checkpoint complex-bound APC/C reveals reciprocal and conformational regulation of ubiquitin ligation. Mol Cell 63:593–607CrossRefPubMedPubMedCentralGoogle Scholar
  371. Yamamoto Y, Matsuyama H, Chochi Y, Okuda M, Kawauchi S, Inoue R, Furuya T, Oga A, Naito K, Sasaki K (2007) Overexpression of BUBR1 is associated with chromosomal instability in bladder cancer. Cancer Genet Cytogenet 174:42–47CrossRefPubMedPubMedCentralGoogle Scholar
  372. Yang Y, Kim AH, Yamada T, Wu B, Bilimoria PM, Ikeuchi Y, de la Iglesia N, Shen J, Bonni AA (2009) Cdc20-APC ubiquitin signaling pathway regulates presynaptic differentiation. Science 326:575–578CrossRefPubMedPubMedCentralGoogle Scholar
  373. Ye Y, Rape M (2009) Building ubiquitin chains: E2 enzymes at work. Nature Rev Mol Cell Biol 10:755–764CrossRefGoogle Scholar
  374. Yi J, Wei X, Li X, Wan L, Dong J, Wang R (2018) A genome-wide comprehensive analysis of alterations in driver genes in non-small-cell lung cancer. Anticancer Drugs 29:10–18CrossRefPubMedPubMedCentralGoogle Scholar
  375. Yu H (2007) Cdc20: a WD40 activator for a cell cycle degradation machine. Mol Cell 27:3–16CrossRefPubMedPubMedCentralGoogle Scholar
  376. Yu H (2002) Regulation of APC-Cdc20 by the spindle checkpoint. Curr Opin Cell Biol 14:706–714CrossRefPubMedPubMedCentralGoogle Scholar
  377. Yu Y, Munger K (2013) Human papillomavirus type 16 E7 oncoprotein inhibits the anaphase promoting complex/cyclosome activity by dysregulating EMI1 expression in mitosis. Virol 446:251–259CrossRefGoogle Scholar
  378. Yudkovsky Y, Shteinberg M, Listovsky T, Brandeis M, Hershko A (2000) Phosphorylation of Cdc20/fizzy negatively regulates the mammalian cyclosome/APC in the mitotic checkpoint. Biochem Biophys Res Commun 271:299–304CrossRefPubMedPubMedCentralGoogle Scholar
  379. Zeng X, King R (2012) An APC/C inhibitor stabilizes cyclin B1 by prematurely terminating ubiquitination. Nat Chem Biol 8:383–392CrossRefPubMedPubMedCentralGoogle Scholar
  380. Zeng X, Sigoillot F, Gaur S, Choi S, Pfaff KL, Oh DC, Hathaway N, Dimova N, Cuny GD, King RW (2010) Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage. Cancer Cell 18:382–395CrossRefPubMedPubMedCentralGoogle Scholar
  381. Zhang S, Chang L, Alfieri C, Zhang Z, Yang J, Maslen S, Skehel M, Barford D (2016) Molecular mechanism of APC/C activation by mitotic phosphorylation. Nature 533:260–264CrossRefPubMedPubMedCentralGoogle Scholar
  382. Zhang J, Cicero S, Wang L, Romito-DiGiacomo R, Yang Y, Herrup K (2008a) Nuclear localization of Cdk5 is a key determinant in the postmitotic state of neurons. Proc Natl Acad Sci USA 105:8772–8777CrossRefGoogle Scholar
  383. Zhang SH, Xu AM, Chen XF, Li DH, Sun MP, Wang YJ (2008b) Clinicopathologic significance of mitotic arrest defective protein 2 overexpression in hepatocellular carcinoma. Hum Pathol 39:1827–1834CrossRefGoogle Scholar
  384. Zhang J, Li H, Zhou T, Zhou J, Herrup K (2012) Cdk5 levels oscillate during the neuronal cell cycle. J Biol Chem 287:25985–25994CrossRefPubMedPubMedCentralGoogle Scholar
  385. Zhang L, Park CH, Wu J, Kim H, Liu W, Fujita T, Balasubramani M, Schreiber EM, Wang XF, Wan Y (2010) Proteolysis of Rad17 by Cdh1/APC regulates checkpoint termination and recovery from genotoxic stress. EMBO J 29:1726–1737CrossRefPubMedPubMedCentralGoogle Scholar
  386. Zhang J, Wan L, Dai X, Sun Y, Wei W (2014) Functional characterization of anaphase promoting complex/cyclosome (APC/C) E3 ubiquitin ligases in tumorigenesis. Biochim et Biophys Acta 1845:277–293Google Scholar
  387. Zhao WM, Coppinger JA, Seki A, Cheng XL, Yates JR, Fang G (2008) RCS1, a substrate of APC/C, controls the metaphase to anaphase transition. Proc Natl Acad Sci USA 105:13415–13420Google Scholar
  388. Zhao WM, Fang G (2005) Anillin is a substrate of anaphase-promoting complex/cyclosome (APC/C) that controls spatial contractility of myosin during late cytokinesis. J Biol Chem 280:33516–33524CrossRefGoogle Scholar
  389. Zhao Y, Tang Q, Ni R, Huang X, Wang Y, Lu C, Shen A, Wang Y, Li C, Yuan Q, Chen H, Cheng C, He S (2013) Early mitotic inhibitor-1, an anaphase-promoting complex/cyclosome inhibitor, can control tumor cell proliferation in hepatocellular carcinoma: correlation with Skp2 stability and degradation of p27Kip1. Hum Path 44:365–373CrossRefPubMedPubMedCentralGoogle Scholar
  390. Zhou Z, He M, Shah A, Wan Y (2016) Insights into APC/C: from cellular function to diseases and therapeutics. Cell Div 11:9CrossRefPubMedPubMedCentralGoogle Scholar
  391. Zhou J, Zhang S, Fu G, He Z, Xu Y, Ye W, Chen Z (2018) Overexpression of APC11 predicts worse survival in lung adenocarcinoma. OncoTargets Ther 11:7125–7132CrossRefGoogle Scholar
  392. Zhu Y, Carvey PM, Ling Z (2006) Age-related changes in glutathione and glutathione-related enzymes in rat brain. Brain Res 1090:35–44CrossRefPubMedPubMedCentralGoogle Scholar
  393. Zhuang L, Yang Z, Meng Z (2018) Upregulation of BUB1B, CCNB1, CDC7, CDC20, and MCM3 in tumor tissues predicted worse overall survival and disease-free survival in hepatocellular carcinoma patients. Biomed Res Int 2018:1–8CrossRefGoogle Scholar
  394. Zich J, Hardwick KG (2010) Getting down to the phosphorylated ‘nuts and bolts’ of spindle checkpoint signalling. Trends Biochem Sci 35:18–27CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Faculty of Health and Life Sciences, Department of Biological and Medical SciencesOxford Brookes UniversityOxfordEngland, UK

Personalised recommendations