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Cell Cycle Regulation by Protein Degradation

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Cell Cycle Control

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1170))

Abstract

Cell division is controlled by a highly regulated program to accurately duplicate and segregate chromosomes. An important feature of the cell cycle regulatory program is that key cell cycle proteins are present and active during specific cell cycle stages but are later removed or inhibited to maintain appropriate timing. The ubiquitin–proteasome system has emerged as an important mechanism to target cell cycle proteins for degradation at critical junctures during cell division. Two key E3 ubiquitin ligase complexes that target key cell cycle proteins are the Skp1–Cul1–F-box protein complex and the anaphase-promoting complex/cyclosome. This chapter focuses on the role of these E3 ubiquitin ligases and how ubiquitin-dependent degradation of central cell cycle regulatory proteins advances the cell cycle.

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References

  1. Wilkinson KD, Urban MK, Haas AL (1980) Ubiquitin is the ATP-dependent proteolysis factor I of rabbit reticulocytes. J Biol Chem 255(16):7529–7532

    CAS  PubMed  Google Scholar 

  2. Ciechanover A, Elias S, Heller H, Hershko A (1982) “Covalent affinity” purification of ubiquitin-activating enzyme. J Biol Chem 257(5):2537–2542

    CAS  PubMed  Google Scholar 

  3. Hershko A, Heller H, Elias S, Ciechanover A (1983) Components of ubiquitin-protein ligase system. Resolution, affinity purification, and role in protein breakdown. J Biol Chem 258(13):8206–8214

    CAS  PubMed  Google Scholar 

  4. Hershko A (1983) Ubiquitin: roles in protein modification and breakdown. Cell 34(1):11–12

    CAS  PubMed  Google Scholar 

  5. Piotrowski J, Beal R, Hoffman L, Wilkinson KD, Cohen RE, Pickart CM (1997) Inhibition of the 26 S proteasome by polyubiquitin chains synthesized to have defined lengths. J Biol Chem 272(38):23712–23721

    CAS  PubMed  Google Scholar 

  6. Finley D (2009) Recognition and processing of ubiquitin-protein conjugates by the proteasome. Annu Rev Biochem 78:477–513

    CAS  PubMed Central  PubMed  Google Scholar 

  7. Tomko RJ Jr, Hochstrasser M (2013) Molecular architecture and assembly of the eukaryotic proteasome. Annu Rev Biochem 82:415–445

    CAS  PubMed  Google Scholar 

  8. Hershko A, Ciechanover A (1998) The ubiquitin system. Annu Rev Biochem 67:425–479

    CAS  PubMed  Google Scholar 

  9. Page AM, Hieter P (1999) The anaphase-promoting complex: new subunits and regulators. Annu Rev Biochem 68:583–609

    CAS  PubMed  Google Scholar 

  10. Deshaies RJ, Joazeiro CAP (2009) RING domain E3 ubiquitin ligases. Annu Rev Biochem 78:399–434

    CAS  PubMed  Google Scholar 

  11. Teixeira LK, Reed SI (2013) Ubiquitin ligases and cell cycle control. Annu Rev Biochem 82:387–414

    CAS  PubMed  Google Scholar 

  12. Bai C, Sen P, Hofmann K, Ma L, Goebl M, Harper JW, Elledge SJ (1996) SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box. Cell 86(2):263–274

    CAS  PubMed  Google Scholar 

  13. Skowyra D, Craig KL, Tyers M, Elledge SJ, Harper JW (1997) F-box proteins are receptors that recruit phosphorylated substrates to the SCF ubiquitin-ligase complex. Cell 91(2):209–219

    CAS  PubMed  Google Scholar 

  14. Feldman RM, Correll CC, Kaplan KB, Deshaies RJ (1997) A complex of Cdc4p, Skp1p, and Cdc53p/cullin catalyzes ubiquitination of the phosphorylated CDK inhibitor Sic1p. Cell 91(2):221–230

    CAS  PubMed  Google Scholar 

  15. Kamura T, Koepp DM, Conrad MN, Skowyra D, Moreland RJ, Iliopoulos O, Lane WS, Kaelin WG Jr, Elledge SJ, Conaway RC, Harper JW, Conaway JW (1999) Rbx1, a component of the VHL tumor suppressor complex and SCF ubiquitin ligase. Science 284(5414): 657–661

    CAS  PubMed  Google Scholar 

  16. Ohta T, Michel JJ, Schottelius AJ, Xiong Y (1999) ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity. Mol Cell 3(4):535–541

    CAS  PubMed  Google Scholar 

  17. Tan P, Fuchs SY, Chen A, Wu K, Gomez C, Ronai Z, Pan ZQ (1999) Recruitment of a ROC1-CUL1 ubiquitin ligase by Skp1 and HOS to catalyze the ubiquitination of I kappa B alpha. Mol Cell 3(4):527–533

    CAS  PubMed  Google Scholar 

  18. Seol JH, Feldman RM, Zachariae W, Shevchenko A, Correll CC, Lyapina S, Chi Y, Galova M, Claypool J, Sandmeyer S, Nasmyth K, Deshaies RJ, Shevchenko A, Deshaies RJ (1999) Cdc53/cullin and the essential Hrt1 RING-H2 subunit of SCF define a ubiquitin ligase module that activates the E2 enzyme Cdc34. Genes Dev 13(12):1614–1626

    CAS  PubMed Central  PubMed  Google Scholar 

  19. Skaar JR, Pagan JK, Pagano M (2013) Mechanisms and function of substrate recruitment by F-box proteins. Nat Rev Mol Cell Biol 14(6):369–381

    CAS  PubMed  Google Scholar 

  20. Zhou P, Howley PM (1998) Ubiquitination and degradation of the substrate recognition subunits of SCF ubiquitin-protein ligases. Mol Cell 2(5):571–580

    CAS  PubMed  Google Scholar 

  21. 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 (6979):190–193

    CAS  PubMed  Google Scholar 

  22. 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(6979):194–198

    CAS  PubMed  Google Scholar 

  23. Visintin R, Prinz S, Amon A (1997) CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science 278(5337):460–463

    CAS  PubMed  Google Scholar 

  24. Peters JM (2006) The anaphase promoting complex/cyclosome: a machine designed to destroy. Nat Rev Mol Cell Biol 7(9):644–656

    CAS  PubMed  Google Scholar 

  25. Sullivan M, Morgan DO (2007) Finishing mitosis, one step at a time. Nat Rev Mol Cell Biol 8(11):894–903

    CAS  PubMed  Google Scholar 

  26. Pesin JA, Orr-Weaver TL (2008) Regulation of APC/C activators in mitosis and meiosis. Annu Rev Cell Dev Biol 24:475–499

    CAS  PubMed  Google Scholar 

  27. Barford D (2011) Structural insights into anaphase-promoting complex function and mechanism. Philos Trans R Soc Lond B Biol Sci 366(1584):3605–3624

    CAS  PubMed Central  PubMed  Google Scholar 

  28. Glotzer M, Murray AW, Kirschner MW (1991) Cyclin is degraded by the ubiquitin pathway. Nature 349(6305):132–138

    CAS  PubMed  Google Scholar 

  29. Pfleger CM, Kirschner MW (2000) The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. Genes Dev 14(6): 655–665

    CAS  PubMed Central  PubMed  Google Scholar 

  30. Zachariae W, Schwab M, Nasmyth K, Seufert W (1998) Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex. Science 282(5394): 1721–1724

    CAS  PubMed  Google Scholar 

  31. 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(5):645–655

    CAS  PubMed  Google Scholar 

  32. Reimann JD, Gardner BE, Margottin-Goguet F, Jackson PK (2001) Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins. Genes Dev 15(24):3278–3285

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Martinez JS, Jeong DE, Choi E, Billings BM, Hall MC (2006) Acm1 is a negative regulator of the CDH1-dependent anaphase-promoting complex/cyclosome in budding yeast. Mol Cell Biol 26(24):9162–9176

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Jin L, Williamson A, Banerjee S, Philipp I, Rape M (2008) Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133(4):653–665

    CAS  PubMed Central  PubMed  Google Scholar 

  35. Mendenhall MD, Jones CA, Reed SI (1987) Dual regulation of the yeast CDC28-p40 protein kinase complex: cell cycle, pheromone, and nutrient limitation effects. Cell 50(6): 927–935

    CAS  PubMed  Google Scholar 

  36. Schneider BL, Yang QH, Futcher AB (1996) Linkage of replication to start by the Cdk inhibitor Sic1. Science 272(5261):560–562

    CAS  PubMed  Google Scholar 

  37. Tyers M (1996) The cyclin-dependent kinase inhibitor p40SIC1 imposes the requirement for Cln G1 cyclin function at start. Proc Natl Acad Sci U S A 93(15):7772–7776

    CAS  PubMed Central  PubMed  Google Scholar 

  38. Verma R, Feldman RM, Deshaies RJ (1997) SIC1 is ubiquitinated in vitro by a pathway that requires CDC4, CDC34, and cyclin/CDK activities. Mol Biol Cell 8(8):1427–1437

    CAS  PubMed Central  PubMed  Google Scholar 

  39. Yu ZK, Gervais JL, Zhang H (1998) Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21(CIP1/WAF1) and cyclin D proteins. Proc Natl Acad Sci U S A 95(19):11324–11329

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Tsvetkov LM, Yeh KH, Lee SJ, Sun H, Zhang H (1999) p27(Kip1) ubiquitination and degradation is regulated by the SCF(Skp2) complex through phosphorylated Thr187 in p27. Curr Biol 9(12):661–664

    CAS  PubMed  Google Scholar 

  41. Carrano AC, Eytan E, Hershko A, Pagano M (1999) SKP2 is required for ubiquitin-mediated degradation of the CDK inhibitor p27. Nat Cell Biol 1(4):193–199

    CAS  PubMed  Google Scholar 

  42. Kamura T, Hara T, Kotoshiba S, Yada M, Ishida N, Imaki H, Hatakeyama S, Nakayama K, Nakayama KI (2003) Degradation of p57Kip2 mediated by SCFSkp2-dependent ubiquitylation. Proc Natl Acad Sci U S A 100(18):10231–10236

    CAS  PubMed Central  PubMed  Google Scholar 

  43. Ganoth D, Bornstein G, Ko TK, Larsen B, Tyers M, Pagano M, Hershko A (2001) The cell-cycle regulatory protein Cks1 is required for SCF(Skp2)-mediated ubiquitinylation of p27. Nat Cell Biol 3(3):321–324

    CAS  PubMed  Google Scholar 

  44. Spruck C, Strohmaier H, Watson M, Smith AP, Ryan A, Krek TW, Reed SI (2001) A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1. Mol Cell 7(3):639–650

    CAS  PubMed  Google Scholar 

  45. Jaspersen SL, Charles JF, Tinker-Kulberg RL, Morgan DO (1998) A late mitotic regulatory network controlling cyclin destruction in Saccharomyces cerevisiae. Mol Biol Cell 9(10): 2803–2817

    CAS  PubMed Central  PubMed  Google Scholar 

  46. Lukas C, Sorensen CS, Kramer E, Santoni-Rugiu E, Lindeneg C, Peters JM, Bartek J, Lukas J (1999) Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex. Nature 401(6755):815–818

    CAS  PubMed  Google Scholar 

  47. Barral Y, Jentsch S, Mann C (1995) G1 cyclin turnover and nutrient uptake are controlled by a common pathway in yeast. Genes Dev 9(4):399–409

    CAS  PubMed  Google Scholar 

  48. Willems AR, Lanker S, Patton EE, Craig KL, Nason TF, Mathias N, Kobayashi R, Wittenberg C, Tyers M (1996) Cdc53 targets phosphorylated G1 cyclins for degradation by the ubiquitin proteolytic pathway. Cell 86(3):453–463

    CAS  PubMed  Google Scholar 

  49. Li FN, Johnston M (1997) Grr1 of Saccharomyces cerevisiae is connected to the ubiquitin proteolysis machinery through Skp1: coupling glucose sensing to gene expression and the cell cycle. Embo J 16(18):5629–5638

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Diehl JA, Zindy F, Sherr CJ (1997) Inhibition of cyclin D1 phosphorylation on threonine-286 prevents its rapid degradation via the ubiquitin-proteasome pathway. Genes Dev 11(8):957–972

    CAS  PubMed  Google Scholar 

  51. Diehl JA, Cheng M, Roussel MF, Sherr CJ (1998) Glycogen synthase kinase-3beta regulates cyclin D1 proteolysis and subcellular localization. Genes Dev 12(22):3499–3511

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Lin DI, Barbash O, Kumar KG, Weber JD, Harper JW, Klein-Szanto AJ, Rustgi A, Fuchs SY, Diehl JA (2006) Phosphorylation-dependent ubiquitination of cyclin D1 by the SCF(FBX4-alphaB crystallin) complex. Mol Cell 24(3):355–366

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Siu KT, Rosner MR, Minella AC (2012) An integrated view of cyclin E function and regulation. Cell Cycle 11(1):57–64

    CAS  PubMed Central  PubMed  Google Scholar 

  54. Koepp DM, Schaefer LK, Ye X, Keyomarsi K, Chu C, Harper JW, Elledge SJ (2001) Phosphorylation-dependent ubiquitination of cyclin E by the SCFFbw7 ubiquitin ligase. Science 294(5540):173–177

    CAS  PubMed  Google Scholar 

  55. Strohmaier H, Spruck CH, Kaiser P, Won KA, Sangfelt O, Reed SI (2001) Human F-box protein hCdc4 targets cyclin E for proteolysis and is mutated in a breast cancer cell line. Nature 413(6853):316–322

    CAS  PubMed  Google Scholar 

  56. Moberg KH, Bell DW, Wahrer DC, Haber DA, Hariharan IK (2001) Archipelago regulates Cyclin E levels in Drosophila and is mutated in human cancer cell lines. Nature 413(6853): 311–316

    CAS  PubMed  Google Scholar 

  57. Welcker M, Singer J, Loeb KR, Grim J, Bloecher A, Gurien-West M, Clurman BE, Roberts JM (2003) Multisite phosphorylation by Cdk2 and GSK3 controls cyclin E degradation. Mol Cell 12(2):381–392

    CAS  PubMed  Google Scholar 

  58. Zhang W, Koepp DM (2006) Fbw7 isoform interaction contributes to cyclin E proteolysis. Mol Cancer Res 4(12):935–943

    CAS  PubMed  Google Scholar 

  59. Welcker M, Clurman BE (2007) Fbw7/hCDC4 dimerization regulates its substrate interactions. Cell Div 2:7

    PubMed Central  PubMed  Google Scholar 

  60. Van Drogen F, Sangfelt O, Malyukova A, Matskova L, Yeh E, Means AR, Reed SI (2006) Ubiquitylation of cyclin E requires the sequential function of SCF complexes containing distinct hCdc4 isoforms. Mol Cell 23(1):37–48

    PubMed  Google Scholar 

  61. Popov N, Herold S, Llamazares M, Schulein C, Eilers M (2007) Fbw7 and Usp28 regulate Myc protein stability in response to DNA damage. Cell Cycle 6(19):2327–2331

    CAS  PubMed  Google Scholar 

  62. Jackson LP, Reed SI, Haase SB (2006) Distinct mechanisms control the stability of the related S-phase cyclins Clb5 and Clb6. Mol Cell Biol 26(6):2456–2466

    CAS  PubMed Central  PubMed  Google Scholar 

  63. Shirayama M, Zachariae W, Ciosk R, Nasmyth K (1998) The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae. Embo J 17(5):1336–1349

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Sclafani RA, Holzen TM (2007) Cell cycle regulation of DNA replication. Annu Rev Genet 41:237–280

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Tanaka T, Knapp D, Nasmyth K (1997) Loading of an Mcm protein onto DNA replication origins is regulated by Cdc6p and CDKs. Cell 90(4):649–660

    CAS  PubMed  Google Scholar 

  66. Donovan S, Harwood J, Drury LS, Diffley JF (1997) Cdc6p-dependent loading of Mcm proteins onto pre-replicative chromatin in budding yeast. Proc Natl Acad Sci U S A 94(11): 5611–5616

    CAS  PubMed Central  PubMed  Google Scholar 

  67. Liang C, Stillman B (1997) Persistent initiation of DNA replication and chromatin-bound MCM proteins during the cell cycle in cdc6 mutants. Genes Dev 11(24):3375–3386

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Aparicio OM, Weinstein DM, Bell SP (1997) Components and dynamics of DNA replication complexes in S. cerevisiae: redistribution of MCM proteins and Cdc45p during S phase. Cell 91(1):59–69

    CAS  PubMed  Google Scholar 

  69. Maiorano D, Moreau J, Mechali M (2000) XCDT1 is required for the assembly of pre-replicative complexes in Xenopus laevis. Nature 404(6778):622–625

    CAS  PubMed  Google Scholar 

  70. Nishitani H, Lygerou Z, Nishimoto T, Nurse P (2000) The Cdt1 protein is required to license DNA for replication in fission yeast. Nature 404(6778):625–628

    CAS  PubMed  Google Scholar 

  71. Diffley JF, Cocker JH, Dowell SJ, Rowley A (1994) Two steps in the assembly of complexes at yeast replication origins in vivo. Cell 78(2): 303–316

    CAS  PubMed  Google Scholar 

  72. Mendez J, Stillman B (2000) Chromatin association of human origin recognition complex, cdc6, and minichromosome maintenance proteins during the cell cycle: assembly of prereplication complexes in late mitosis. Mol Cell Biol 20(22):8602–8612

    CAS  PubMed Central  PubMed  Google Scholar 

  73. Drury LS, Perkins G, Diffley JF (1997) The Cdc4/34/53 pathway targets Cdc6p for proteolysis in budding yeast. Embo J 16(19): 5966–5976

    CAS  PubMed Central  PubMed  Google Scholar 

  74. Drury LS, Perkins G, Diffley JFX (2000) The cyclin-dependent kinase Cdc28p regulates distinct modes of Cdc6p proteolysis during the budding yeast cell cycle. Curr Biol 10(5): 231–240

    CAS  PubMed  Google Scholar 

  75. Kim DH, Zhang W, Koepp DM (2012) The Hect domain E3 ligase Tom1 and the F-box protein Dia2 control Cdc6 degradation in G1 phase. J Biol Chem 287(53):44212–44220

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Petersen BO, Wagener C, Marinoni F, Kramer ER, Melixetian M, Lazzerini Denchi E, Gieffers C, Matteucci C, Peters JM, Helin K (2000) Cell cycle- and cell growth-regulated proteolysis of mammalian CDC6 is dependent on APC-CDH1. Genes Dev 14(18):2330–2343

    CAS  PubMed Central  PubMed  Google Scholar 

  77. Mailand N, Diffley JF (2005) CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. Cell 122(6):915–926

    CAS  PubMed  Google Scholar 

  78. Li X, Zhao Q, Liao R, Sun P, Wu X (2003) The SCF(Skp2) ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation. J Biol Chem 278(33):30854–30858

    CAS  PubMed  Google Scholar 

  79. Arias EE, Walter JC (2006) PCNA functions as a molecular platform to trigger Cdt1 destruction and prevent re-replication. Nat Cell Biol 8(1):84–90

    CAS  PubMed  Google Scholar 

  80. Senga T, Sivaprasad U, Zhu W, Park JH, Arias EE, Walter JC, Dutta A (2006) PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. J Biol Chem 281(10):6246–6252

    CAS  PubMed  Google Scholar 

  81. Nishitani H, Sugimoto N, Roukos V, Nakanishi Y, Saijo M, Obuse C, Tsurimoto T, Nakayama KI, Nakayama K, Fujita M, Lygerou Z, Nishimoto T (2006) Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target human Cdt1 for proteolysis. Embo J 25(5):1126–1136

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Mendez J, Zou-Yang XH, Kim SY, Hidaka M, Tansey WP, Stillman B (2002) Human origin recognition complex large subunit is degraded by ubiquitin-mediated proteolysis after initiation of DNA replication. Mol Cell 9(3):481–491

    CAS  PubMed  Google Scholar 

  83. McGarry TJ, Kirschner MW (1998) Geminin, an inhibitor of DNA replication, is degraded during mitosis. Cell 93(6):1043–1053

    CAS  PubMed  Google Scholar 

  84. Wohlschlegel JA, Dwyer BT, Dhar SK, Cvetic C, Walter JC, Dutta A (2000) Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science 290(5500):2309–2312

    CAS  PubMed  Google Scholar 

  85. Russell P, Nurse P (1987) Negative regulation of mitosis by wee1+, a gene encoding a protein kinase homolog. Cell 49(4):559–567

    CAS  PubMed  Google Scholar 

  86. Michael WM, Newport J (1998) Coupling of mitosis to the completion of S phase through Cdc34-mediated degradation of Wee1. Science 282(5395):1886–1889

    CAS  PubMed  Google Scholar 

  87. Watanabe N, Arai H, Nishihara Y, Taniguchi M, Watanabe N, Hunter T, Osada H (2004) M-phase kinases induce phospho-dependent ubiquitination of somatic Wee1 by SCFbeta-TrCP. Proc Natl Acad Sci U S A 101(13): 4419– 4424

    CAS  PubMed Central  PubMed  Google Scholar 

  88. Ayad NG, Rankin S, Murakami M, Jebanathirajah J, Gygi S, Kirschner MW (2003) Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC. Cell 113(1): 101–113

    CAS  PubMed  Google Scholar 

  89. Raspelli E, Cassani C, Lucchini G, Fraschini R (2011) Budding yeast Dma1 and Dma2 participate in regulation of Swe1 levels and localization. Mol Biol Cell 22(13):2185–2197

    CAS  PubMed Central  PubMed  Google Scholar 

  90. King K, Kang H, Jin M, Lew DJ (2013) Feedback control of Swe1p degradation in the yeast morphogenesis checkpoint. Mol Biol Cell 24(7):914–922

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Guardavaccaro D, Kudo Y, Boulaire J, Barchi M, Busino L, Donzelli M, Margottin-Goguet F, Jackson PK, Yamasaki L, Pagano M (2003) Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo. Dev Cell 4(6):799–812

    CAS  PubMed  Google Scholar 

  92. Margottin-Goguet F, Hsu JY, Loktev A, Hsieh HM, Reimann JD, Jackson PK (2003) Prophase destruction of Emi1 by the SCF (betaTrCP/Slimb) ubiquitin ligase activates the anaphase promoting complex to allow progression beyond prometaphase. Dev Cell 4(6): 813–826

    Google Scholar 

  93. Moshe Y, Boulaire J, Pagano M, Hershko A (2004) Role of Polo-like kinase in the degradation of early mitotic inhibitor 1, a regulator of the anaphase promoting complex/cyclosome. Proc Natl Acad Sci U S A 101(21):7937–7942

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Hansen DV, Loktev AV, Ban KH, Jackson PK (2004) Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. Mol Biol Cell 15(12):5623–5634

    CAS  PubMed Central  PubMed  Google Scholar 

  95. King RW, Peters JM, Tugendreich S, Rolfe M, Hieter P, Kirschner MW (1995) A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 81(2):279–288

    CAS  PubMed  Google Scholar 

  96. Sudakin V, Ganoth D, Dahan A, Heller H, Hershko J, Luca FC, Ruderman JV, Hershko A (1995) The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Mol Biol Cell 6(2):185–197

    CAS  PubMed Central  PubMed  Google Scholar 

  97. 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(24):3081–3093

    CAS  PubMed  Google Scholar 

  98. Holloway SL, Glotzer M, King RW, Murray AW (1993) Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor. Cell 73(7):1393–1402

    CAS  PubMed  Google Scholar 

  99. Hershko A, Ganoth D, Sudakin V, Dahan A, Cohen LH, Luca FC, Ruderman JV, Eytan E (1994) Components of a system that ligates cyclin to ubiquitin and their regulation by the protein kinase cdc2. J Biol Chem 269(7):4940–4946

    CAS  PubMed  Google Scholar 

  100. Seufert W, Futcher B, Jentsch S (1995) Role of a ubiquitin-conjugating enzyme in degradation of S- and M-phase cyclins. Nature 373(6509):78–81

    CAS  PubMed  Google Scholar 

  101. Uhlmann F, Lottspeich F, Nasmyth K (1999) Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1. Nature 400(6739):37–42

    CAS  PubMed  Google Scholar 

  102. 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(6):1067–1076

    CAS  PubMed  Google Scholar 

  103. Jager H, Herzig A, Lehner CF, Heidmann S (2001) Drosophila separase is required for sister chromatid separation and binds to PIM and THR. Genes Dev 15(19):2572–2584

    CAS  PubMed Central  PubMed  Google Scholar 

  104. Waizenegger IC, Hauf S, Meinke A, Peters JM (2000) Two distinct pathways remove mammalian cohesin from chromosome arms in prophase and from centromeres in anaphase. Cell 103(3):399–410

    CAS  PubMed  Google Scholar 

  105. Fang G, Yu H, Kirschner MW (1998) Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. Mol Cell 2(2):163–171

    CAS  PubMed  Google Scholar 

  106. Prinz S, Hwang ES, Visintin R, Amon A (1998) The regulation of Cdc20 proteolysis reveals a role for APC components Cdc23 and Cdc27 during S phase and early mitosis. Curr Biol 8(13):750–760

    CAS  PubMed  Google Scholar 

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Acknowledgments

The author’s research has been supported by the National Institutes of Health (R01 GM076663).

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Correspondence to Deanna M. Koepp .

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Koepp, D.M. (2014). Cell Cycle Regulation by Protein Degradation. In: Noguchi, E., Gadaleta, M. (eds) Cell Cycle Control. Methods in Molecular Biology, vol 1170. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-0888-2_4

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