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The ubiquitin-proteasome pathway in cell cycle control

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Cell Cycle Regulation

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 42))

Abstract

Ubiquitin-mediated proteolysis is one of the key mechanisms underlying cell cycle control. The removal of barriers posed by accumulation of negative regulators, as well as the clearance of proteins when they are no longer needed or deleterious, are carried out via the ubiquitin-proteasome system. Ubiquitin conjugating enzymes and protein-ubiquitin ligases collaborate to mark proteins destined for degradation by the proteasome by covalent attachment of multi-ubiquitin chains. Most regulated proteolysis during the cell cycle can be attributed to two families of protein-ubiquitin ligases. The anaphase promoting complex/cyclosome (APC/C) is activated during mitosis and G1 where it is responsible for eliminating proteins that impede mitotic progression and that would have deleterious consequences if allowed to accumulate during G1. SCF (Skp1/Culin/F-box protein) protein-ubiquitin ligases ubiquitylate proteins that are marked by phosphorylation at specific sequences known as phosphodegrons. Targeting of proteins for destruction by phosphorylation provides a mechanism for linking cell cycle regulation to internal and external signaling pathways via regulated protein kinase activities.

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References

  1. Agarwal R, Tang Z, Yu H, Cohen-Fix O (2003) Two distinct pathways for inhibiting pds1 ubiquitination in response to DNA damage. J Biol Chem 278:45027–44033

    PubMed  CAS  Google Scholar 

  2. Alexandru G, Uhlmann F, Mechtler K, Poupart MA, Nasmyth K (2001) Phosphorylation of the cohesin subunit Scc1 by Polo/Cdc5 kinase regulates sister chromatid separation in yeast. Cell 105:459–472

    PubMed  CAS  Google Scholar 

  3. Amerik AY, Li SJ, Hochstrasser M (2000) Analysis of the deubiquitinating enzymes of the yeast Saccharomyces cerevisiae. Biol Chem 381:981–992

    PubMed  CAS  Google Scholar 

  4. 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 86:263–274

    PubMed  CAS  Google Scholar 

  5. Banin S, Moyal L, Shieh S, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, Ziv Y (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281:1674–1677

    PubMed  CAS  Google Scholar 

  6. Barak Y, Juven T, Haffner R, Oren M (1993) mdm2 expression is induced by wild type p53 activity. Embo J 12:461–468

    PubMed  CAS  Google Scholar 

  7. Barbey R, Baudouin-Cornu P, Lee TA, Rouillon A, Zarzov P, Tyers M, Thomas D (2005) Inducible dissociation of SCFMet30 ubiquitin ligase mediates a rapid transcriptional response to cadmium. EMBO J 24:521–532

    PubMed  CAS  Google Scholar 

  8. Bashir T, Dorrello NV, Amador V, Guardavaccaro D, Pagano M (2004) Control of the SCFSkp2-Cks1 ubiquitin ligase by the APC/CCdh1 ubiquitin ligase. Nature 428:190–193

    PubMed  CAS  Google Scholar 

  9. Bhattacharya S, Garriga J, Calbo J, Yong T, Haines DS, Grana X (2003) SKP2 associates with p130 and accelerates p130 ubiquitylation and degradation in human cells. Oncogene 22:2443–2451

    PubMed  CAS  Google Scholar 

  10. Bocca SN, Muzzopappa M, Silberstein S, Wappner P (2001) Occurrence of a putative SCF ubiquitin ligase complex in Drosophila. Biochem Biophys Res Commun 286:357–364

    PubMed  CAS  Google Scholar 

  11. Bornstein G, Bloom J, Sitry-Shevah D, Nakayama K, Pagano M, Hershko A (2003) Role of SCFSkp2 ubiquitin ligase in the degradation of p21Cip1 during S-phase. J Biol Chem 278:25752–25757

    PubMed  CAS  Google Scholar 

  12. Busino L, Donzelli M, Chiesa M, Guardavaccaro D, Ganoth D, Dorrello NV, Hershko A, Pagano M, Draetta GF (2003) Degradation of Cdc25A by beta-TrCP during S phase and in response to DNA damage. Nature 426:87–91

    PubMed  CAS  Google Scholar 

  13. Calhoun ES, Jones JB, Ashfaq R, Adsay V, Baker SJ, Valentine V, Hempen PM, Hilgers W, Yeo CJ, Hruban RH, Kern SE (2003) BRAF and FBXW7 (CDC4, FBW7, AGO, SEL10) mutations in distinct subsets of pancreatic cancer: potential therapeutic targets. Am J Pathol 163:1255–1260

    PubMed  CAS  Google Scholar 

  14. Canman CE, Lim DS, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano JD (1998) Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281:1677–1679

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  16. Chan GK, Yen TJ (2003) The mitotic checkpoint: a signaling pathway that allows a single unattached kinetochore to inhibit mitotic exit. Prog Cell Cycle Res 5:431–439

    PubMed  Google Scholar 

  17. Chan GK, Jablonski SA, Sudakin V, Hittle JC, Yen TJ (1999) Human BUBR1 is a mitotic checkpoint kinase that monitors CENP-E functions at kinetochores and binds the cyclosome/APC. J Cell Biol 146:941–954

    PubMed  CAS  Google Scholar 

  18. Chan GK, Jablonski SA, Starr DA, Goldberg ML, Yen TJ (2000) Human Zw10 and ROD are mitotic checkpoint proteins that bind to kinetochores. Nat Cell Biol 2:944–947

    PubMed  CAS  Google Scholar 

  19. Chen J, Marechal V, Levine AJ (1993) Mapping of the p53 and mdm-2 interaction domains. Mol Cell Biol 13:4107–4114

    PubMed  CAS  Google Scholar 

  20. Chen RH, Waters JC, Salmon ED, Murray AW (1996) Association of spindle assembly checkpoint component XMAD2 with unattached kinetochores. Science 274:242–246

    PubMed  CAS  Google Scholar 

  21. Chen Z, Pickart CM (1990) A 25-kilodalton ubiquitin carrier protein (E2) catalyzes multi-ubiquitin chain synthesis via lysine 48 of ubiquitin. J Biol Chem 265:21835–21842

    PubMed  CAS  Google Scholar 

  22. 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 93:1067–1076

    PubMed  CAS  Google Scholar 

  23. Clarke DJ, Mondesert G, Segal M, Bertolaet BL, Jensen S, Wolff M, Henze M, Reed SI (2001a) Dosage suppressors of pds1 implicate ubiquitin-associated domains in checkpoint control. Mol Cell Biol 21:1997–2007

    PubMed  CAS  Google Scholar 

  24. Clarke DJ, Segal M, Jensen S, Reed SI (2001b) Mec1p regulates Pds1p levels in S phase: complex coordination of DNA replication and mitosis. Nat Cell Biol 3:619–627

    PubMed  CAS  Google Scholar 

  25. Clarke DJ, Segal M, Andrews CA, Rudyak SG, Jensen S, Smith K, Reed SI (2003) S-phase checkpoint controls mitosis via an APC-independent Cdc20p function. Nat Cell Biol 5:928–935

    PubMed  CAS  Google Scholar 

  26. Cohen-Fix O, Koshland D (1997) The anaphase inhibitor of Saccharomyces cerevisiae Pds1p is a target of the DNA damage checkpoint pathway. Proc Natl Acad Sci USA 94:14361–14366

    PubMed  CAS  Google Scholar 

  27. 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 10:3081–3093

    PubMed  CAS  Google Scholar 

  28. Connelly C, Hieter P (1996) Budding yeast SKP1 encodes an evolutionarily conserved kinetochore protein required for cell cycle progression. Cell 86:275–285

    PubMed  CAS  Google Scholar 

  29. Davis ES, Wille L, Chestnut BA, Sadler PL, Shakes DC, Golden A (2002) Multiple subunits of the Caenorhabditis elegans anaphase-promoting complex are required for chromosome segregation during meiosis I. Genetics 160:805–813

    PubMed  CAS  Google Scholar 

  30. den Elzen N, Pines J (2001) Cyclin A is destroyed in prometaphase and can delay chromosome alignment and anaphase. J Cell Biol 153:121–136

    Google Scholar 

  31. Donzelli M, Busino L, Chiesa M, Ganoth D, Hershko A, Draetta GF (2004) Hierarchical order of phosphorylation events commits Cdc25A to betaTrCP-dependent degradation. Cell Cycle 3:469–471

    PubMed  CAS  Google Scholar 

  32. Donzelli M, Squatrito M, Ganoth D, Hershko A, Pagano M, Draetta GF (2002) Dual mode of degradation of Cdc25 A phosphatase. EMBO J 21:4875–4884

    PubMed  CAS  Google Scholar 

  33. Draetta G, Luca F, Westendorf J, Brizuela L, Ruderman J, Beach D (1989) Cdc2 protein kinase is complexed with both cyclin A and B: evidence for proteolytic inactivation of MPF. Cell 56:829–838

    PubMed  CAS  Google Scholar 

  34. Dulic V, Kaufmann WK, Wilson SJ, Tlsty TD, Lees E, Harper JW, Elledge SJ, Reed SI (1994) p53-dependent inhibition of cyclin-dependent kinase activities in human fibroblasts during radiation-induced G1 arrest. Cell 76:1013–1023

    PubMed  CAS  Google Scholar 

  35. Ekholm-Reed S, Mendez J, Tedesco D, Zetterberg A, Stillman B, Reed SI (2004) Deregulation of cyclin E in human cells interferes with prereplication complex assembly. J Cell Biol 165:789–800

    PubMed  CAS  Google Scholar 

  36. el-Deiry WS, Harper JW, PM OC, Velculescu VE, Canman CE, Jackman J, Pietenpol JA, Burrell M, Hill DE, Wang Y et al. (1994) WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 54:1169–1174

    PubMed  CAS  Google Scholar 

  37. Elsasser S, Chandler-Militello D, Muller B, Hanna J, Finley D (2004) Rad23 and Rpn10 serve as alternative ubiquitin receptors for the proteasome. J Biol Chem 279:26817–26822

    PubMed  CAS  Google Scholar 

  38. Evans T, Rosenthal ET, Youngblom J, Distel D, Hunt T (1983) Cyclin: a protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division. Cell 33:389–396

    PubMed  CAS  Google Scholar 

  39. Fang G, Yu H, Kirschner MW (1998) The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes Dev 12:1871–1883

    PubMed  CAS  Google Scholar 

  40. Fang G, Yu H, Kirschner MW (1999) Control of mitotic transitions by the anaphase-promoting complex. Philos Trans R Soc Lond B Biol Sci 354:1583–1590

    PubMed  CAS  Google Scholar 

  41. Fang S, Jensen JP, Ludwig RL, Vousden KH, Weissman AM (2000) Mdm2 is a RING finger-dependent ubiquitin protein ligase for itself and p53. J Biol Chem 275:8945–8951

    PubMed  CAS  Google Scholar 

  42. 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 91:221–230

    PubMed  CAS  Google Scholar 

  43. Ferdous A, Gonzalez F, Sun L, Kodadek T, Johnston SA (2001) The 19S regulatory particle of the proteasome is required for efficient transcription elongation by RNA polymerase II. Mol Cell 7:981–991

    PubMed  CAS  Google Scholar 

  44. Ferdous A, Kodadek T, Johnston SA (2002) A nonproteolytic function of the 19S regulatory subunit of the 26S proteasome is required for efficient activated transcription by human RNA polymerase II. Biochemistry 41:12798–12805

    CAS  Google Scholar 

  45. Flick K, Ouni I, Wohlschlegel JA, Capati C, McDonald WH, Yates JR, Kaiser P (2004) Proteolysis-independent regulation of the transcription factor Met4 by a single Lys 48-linked ubiquitin chain. Nat Cell Biol 6:634–641

    PubMed  CAS  Google Scholar 

  46. Fuchs SY, Chen A, Xiong Y, Pan ZQ, Ronai Z (1999) HOS, a human homolog of Slimb, forms an SCF complex with Skp1 and Cullin1 and targets the phosphorylation-dependent degradation of IkappaB and beta-catenin. Oncogene 18:2039–2046

    PubMed  CAS  Google Scholar 

  47. Ganoth D, Bornstein G, Ko TK, Larsen B, Tyers M, Pagano M, Hershko A (2001) The cell-cycle regulatory protein Cks1 is required for SCFSkp2-mediated ubiquitinylation of p27. Nat Cell Biol 3:321–324

    PubMed  CAS  Google Scholar 

  48. 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 153:137–148

    PubMed  CAS  Google Scholar 

  49. Ghiara JB, Richardson HE, Sugimoto K, Henze M, Lew DJ, Wittenberg C, Reed SI (1991) A cyclin B homolog in S. cerevisiae: chronic activation of the Cdc28 protein kinase by cyclin prevents exit from mitosis. Cell 65:163–174

    PubMed  CAS  Google Scholar 

  50. Ghislain M, Udvardy A, Mann C (1993) S. cerevisiae 26S protease mutants arrest cell division in G2/metaphase. Nature 366:358–362

    PubMed  CAS  Google Scholar 

  51. Gieffers C, Dube P, Harris JR, Stark H, Peters JM (2001) Three-dimensional structure of the anaphase-promoting complex. Mol Cell 7:907–913

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  53. Goebl MG, Yochem J, Jentsch S, McGrath JP, Varshavsky A, Byers B (1988) The yeast cell cycle gene CDC34 encodes a ubiquitin-conjugating enzyme. Science 241:1331–1335

    PubMed  CAS  Google Scholar 

  54. Goh PY, Surana U (1999) Cdc4, a protein required for the onset of S phase, serves an essential function during G2/M transition in Saccharomyces cerevisiae. Mol Cell Biol 19:5512–5522

    PubMed  CAS  Google Scholar 

  55. Goloudina A, Yamaguchi H, Chervyakova DB, Appella E, Fornace AJ, Jr, Bulavin DV (2003) Regulation of human Cdc25A stability by Serine 75 phosphorylation is not sufficient to activate a S phase checkpoint. Cell Cycle 2:473–478

    PubMed  CAS  Google Scholar 

  56. Grossberger R, Gieffers C, Zachariae W, Podtelejnikov AV, Schleiffer A, Nasmyth K, Mann M, Peters JM (1999) Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex. J Biol Chem 274:14500–14507

    PubMed  CAS  Google Scholar 

  57. 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 4:799–812

    PubMed  CAS  Google Scholar 

  58. Gupta-Rossi N, Le Bail O, Gonen H, Brou C, Logeat F, Six E, Ciechanover A, Israel A (2001) Functional interaction between SEL-10, an F-box protein, and the nuclear form of activated Notch1 receptor. J Biol Chem 276:34371–34378

    PubMed  CAS  Google Scholar 

  59. 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 15:5623–5634

    PubMed  CAS  Google Scholar 

  60. Haracska L, Torres-Ramos CA, Johnson RE, Prakash S, Prakash L (2004) Opposing effects of ubiquitin conjugation and SUMO modification of PCNA on replicational bypass of DNA lesions in Saccharomyces cerevisiae. Mol Cell Biol 24:4267–4274

    PubMed  CAS  Google Scholar 

  61. Hardwick KG, Johnston RC, Smith DL, Murray AW (2000) MAD3 encodes a novel component of the spindle checkpoint which interacts with Bub3p, Cdc20p, and Mad2p. J Cell Biol 148:871–882

    PubMed  CAS  Google Scholar 

  62. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ (1993) The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 75:805–816

    PubMed  CAS  Google Scholar 

  63. Harrison C, Katayama S, Dhut S, Chen D, Jones N, Bahler J, Toda T (2005) SCFPof1-ubiquitin and its target Zip1 transcription factor mediate cadmium response in fission yeast. EMBO J 24:599–610

    PubMed  CAS  Google Scholar 

  64. Hartwell LH, Culotti J, Pringle JR, Reid BJ (1974) Genetic control of the cell division cycle in yeast. Science 183:46–51

    PubMed  CAS  Google Scholar 

  65. Hassepass I, Voit R, Hoffmann I (2003) Phosphorylation at serine 75 is required for UV-mediated degradation of human Cdc25A phosphatase at the S-phase checkpoint. J Biol Chem 278:29824–29829

    PubMed  CAS  Google Scholar 

  66. Hatakeyama S, Yada M, Matsumoto M, Ishida N, Nakayama KI (2001) U box proteins as a new family of ubiquitin–protein ligases. J Biol Chem 276:33111–33120

    PubMed  CAS  Google Scholar 

  67. Hattori K, Hatakeyama S, Shirane M, Matsumoto M, Nakayama K (1999) Molecular dissection of the interactions among IkappaBalpha, FWD1, and Skp1 required for ubiquitin-mediated proteolysis of IkappaBalpha. J Biol Chem 274:29641–29647

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  69. Hilioti Z, Chung YS, Mochizuki Y, Hardy CF, Cohen-Fix O (2001) The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner. Curr Biol 11:1347–1352

    PubMed  CAS  Google Scholar 

  70. Hoege C, Pfander B, Moldovan GL, Pyrowolakis G, Jentsch S (2002) RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419:135–141

    PubMed  CAS  Google Scholar 

  71. Honda R, Yasuda H (2000) Activity of MDM2, a ubiquitin ligase, toward p53 or itself is dependent on the RING finger domain of the ligase. Oncogene 19:1473–1476

    PubMed  CAS  Google Scholar 

  72. Honda R, Tanaka H, Yasuda H (1997) Oncoprotein MDM2 is a ubiquitin ligase E3 for tumor suppressor p53. FEBS Lett 420:25–27

    PubMed  CAS  Google Scholar 

  73. Hornig NC, Knowles PP, McDonald NQ, Uhlmann F (2002) The dual mechanism of separase regulation by securin. Curr Biol 12:973–982

    PubMed  CAS  Google Scholar 

  74. Hsiung YG, Chang HC, Pellequer JL, La Valle R, Lanker S, Wittenberg C (2001) F-box protein Grr1 interacts with phosphorylated targets via the cationic surface of its leucine-rich repeat. Mol Cell Biol 21:2506–2520

    PubMed  CAS  Google Scholar 

  75. Hsu JY, Reimann JD, Sorensen CS, Lukas J, Jackson PK (2002) E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APCCdh1. Nat Cell Biol 4:358–366

    PubMed  CAS  Google Scholar 

  76. Hunt T, Luca FC, Ruderman JV (1992) The requirements for protein synthesis and degradation, and the control of destruction of cyclins A and B in the meiotic and mitotic cell cycles of the clam embryo. J Cell Biol 116:707–724

    PubMed  CAS  Google Scholar 

  77. Hwang LH, Lau LF, Smith DL, Mistrot CA, Hardwick KG, Hwang ES, Amon A, Murray AW (1998) Budding yeast Cdc20: a target of the spindle checkpoint. Science 279:1041–1044

    PubMed  CAS  Google Scholar 

  78. Jablonski SA, Chan GK, Cooke CA, Earnshaw WC, Yen TJ (1998) The hBUB1 and hBUBR1 kinases sequentially assemble onto kinetochores during prophase with hBUBR1 concentrating at the kinetochore plates in mitosis. Chromosoma 107:386–396

    PubMed  CAS  Google Scholar 

  79. Jaquenoud M, Gulli MP, Peter K, Peter M (1998) The Cdc42p effector Gic2p is targeted for ubiquitin-dependent degradation by the SCFGrr1 complex. Embo J 17:5360–5373

    PubMed  CAS  Google Scholar 

  80. Jensen S, Segal M, Clarke DJ, Reed SI (2001) A novel role of the budding yeast separin Esp1 in anaphase spindle elongation: evidence that proper spindle association of Esp1 is regulated by Pds1. J Cell Biol 152:27–40

    PubMed  CAS  Google Scholar 

  81. Jin J, Shirogane T, Xu L, Nalepa G, Qin J, Elledge SJ, Harper JW (2003) SCFβ-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase. Genes Dev 17:3062–3074

    PubMed  CAS  Google Scholar 

  82. Kaiser P, Sia RA, Bardes EG, Lew DJ, Reed SI (1998) Cdc34 and the F-box protein Met30 are required for degradation of the Cdk-inhibitory kinase Swe1. Genes Dev 12:2587–2597

    PubMed  CAS  Google Scholar 

  83. Kaiser P, Flick K, Wittenberg C, Reed SI (2000) Regulation of transcription by ubiquitination without proteolysis: Cdc34/SCFMet30-mediated inactivation of the transcription factor Met4. Cell 102:303–314

    PubMed  CAS  Google Scholar 

  84. Kallio M, Weinstein J, Daum JR, Burke DJ, Gorbsky GJ (1998) Mammalian p55CDC mediates association of the spindle checkpoint protein Mad2 with the cyclosome/anaphase-promoting complex, and is involved in regulating anaphase onset and late mitotic events. J Cell Biol 141:1393–1406

    PubMed  CAS  Google Scholar 

  85. Kimura T, Gotoh M, Nakamura Y, Arakawa H (2003) hCDC4b, a regulator of cyclin E, as a direct transcriptional target of p53. Cancer Sci 94:431–436

    PubMed  CAS  Google Scholar 

  86. 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 81:279–288

    PubMed  CAS  Google Scholar 

  87. King RW, Glotzer M, Kirschner MW (1996) Mutagenic analysis of the destruction signal of mitotic cyclins and structural characterization of ubiquitinated intermediates. Mol Biol Cell 7:1343–1357

    PubMed  CAS  Google Scholar 

  88. Kishi T, Seno T, Yamao F (1998) Grr1 functions in the ubiquitin pathway in Saccharomyces cerevisiae through association with Skp1. Mol Gen Genet 257:143–138

    Google Scholar 

  89. Knuutila S, Aalto Y, Autio K, Bjorkqvist AM, El-Rifai W, Hemmer S, Huhta T, Kettunen E, Kiuru-Kuhlefelt S, Larramendy ML, Lushnikova T, Monni O, Pere H, Tapper J, Tarkkanen M, Varis A, Wasenius VM, Wolf M, Zhu Y (1999) DNA copy number losses in human neoplasms. Am J Pathol 155:683–694

    PubMed  CAS  Google Scholar 

  90. Kobe B, Deisenhofer J (1994) The leucine-rich repeat: a versatile binding motif. Trends Biochem Sci 19:415–421

    PubMed  CAS  Google Scholar 

  91. Kobe B, Deisenhofer J (1995) Proteins with leucine-rich repeats. Curr Opin Struct Biol 5:409–416

    PubMed  CAS  Google Scholar 

  92. Koegl M, Hoppe T, Schlenker S, Ulrich HD, Mayer TU, Jentsch S (1999) A novel ubiquitination factor, E4, is involved in multiubiquitin chain assembly. Cell 96:635–644

    PubMed  CAS  Google Scholar 

  93. 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 294:173–177

    PubMed  CAS  Google Scholar 

  94. Kominami K, Toda T (1997) Fission yeast WD-repeat protein pop1 regulates genome ploidy through ubiquitin–proteasome-mediated degradation of the CDK inhibitor Rum1 and the S-phase initiator Cdc18. Genes Dev 11:1548–1560

    PubMed  CAS  Google Scholar 

  95. Kominami K, Ochotorena I, Toda T (1998) Two F-box/WD-repeat proteins Pop1 and Pop2 form hetero- and homo-complexes together with cullin-1 in the fission yeast SCF (Skp1-Cullin-1-F-box) ubiquitin ligase. Genes Cells 3:721–735

    PubMed  CAS  Google Scholar 

  96. Kondo T, Kobayashi M, Tanaka J, Yokoyama A, Suzuki S, Kato N, Onozawa M, Chiba K, Hashino S, Imamura M, Minami Y, Minamino N, Asaka M (2004) Rapid degradation of Cdt1 upon UV-induced DNA damage is mediated by SCFSkp2 complex. J Biol Chem 279:27315–27319

    PubMed  CAS  Google Scholar 

  97. 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 22:6598–6609

    PubMed  CAS  Google Scholar 

  98. Kroll M, Margottin F, Kohl A, Renard P, Durand H, Concordet JP, Bachelerie F, Arenzana-Seisdedos F, Benarous R (1999) Inducible degradation of IkappaBalpha by the proteasome requires interaction with the F-box protein h-betaTrCP. J Biol Chem 274:7941–7945

    PubMed  CAS  Google Scholar 

  99. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274:948–953

    PubMed  CAS  Google Scholar 

  100. Lamb JR, Michaud WA, Sikorski RS, Hieter PA (1994) Cdc16p, Cdc23p and Cdc27p form a complex essential for mitosis. EMBO J 13:4321–4328

    PubMed  CAS  Google Scholar 

  101. Latres E, Chiaur DS, Pagano M (1999) The human F box protein beta-Trcp associates with the Cul1/Skp1 complex and regulates the stability of beta-catenin. Oncogene 18:849–854

    PubMed  CAS  Google Scholar 

  102. Lengronne A, Schwob E (2002) The yeast CDK inhibitor Sic1 prevents genomic instability by promoting replication origin licensing in late G1. Mol Cell 9:1067–1078

    PubMed  CAS  Google Scholar 

  103. Lew DJ, Burke DJ (2003) The spindle assembly and spindle position checkpoints. Annu Rev Genet 37:251–282

    PubMed  CAS  Google Scholar 

  104. 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 16:5629–5638

    PubMed  CAS  Google Scholar 

  105. Li X, Zhao Q, Liao R, Sun P, Wu X (2003) The SCFSkp2 ubiquitin ligase complex interacts with the human replication licensing factor Cdt1 and regulates Cdt1 degradation. J Biol Chem 278:30854–30858

    PubMed  CAS  Google Scholar 

  106. Liu E, Li X, Yan F, Zhao Q, Wu X (2004) Cyclin-dependent kinases phosphorylate human Cdt1 and induce its degradation. J Biol Chem 279:17283–17288

    PubMed  CAS  Google Scholar 

  107. Lisztwan J, Marti A, Sutterluty H, Gstaiger M, Wirbelauer C, Krek W (1998) Association of human CUL-1 and ubiquitin-conjugating enzyme CDC34 with the F-box protein p45SKP2: evidence for evolutionary conservation in the subunit composition of the CDC34-SCF pathway. EMBO J 17:368–383

    PubMed  CAS  Google Scholar 

  108. 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 16:2274–2285

    PubMed  CAS  Google Scholar 

  109. Lorick KL, Jensen JP, Fang S, Ong AM, Hatakeyama S, Weissman AM (1999) RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. Proc Natl Acad Sci USA 96:11364–11369

    PubMed  CAS  Google Scholar 

  110. 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 401:815–818

    PubMed  CAS  Google Scholar 

  111. Lyapina SA, Correll CC, Kipreos ET, Deshaies RJ (1998) Human CUL1 forms an evolutionarily conserved ubiquitin ligase complex (SCF) with SKP1 and an F-box protein. Proc Natl Acad Sci USA 95:7451–7456

    PubMed  CAS  Google Scholar 

  112. Mai S, Mushinski JF (2003) c-Myc-induced genomic instability. J Environ Pathol Toxicol Oncol 22:179–199

    PubMed  CAS  Google Scholar 

  113. Mailand N, Podtelejnikov AV, Groth A, Mann M, Bartek J, Lukas J (2002) Regulation of G2/M events by Cdc25A through phosphorylation-dependent modulation of its stability. EMBO J 21:5911–5920

    PubMed  CAS  Google Scholar 

  114. Mao JH, Perez-Losada J, Wu D, Delrosario R, Tsunematsu R, Nakayama KI, Brown K, Bryson S, Balmain A (2004) Fbxw7/Cdc4 is a p53-dependent, haploinsufficient tumour suppressor gene. Nature 432:775–779

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  116. Maya R, Balass M, Kim ST, Shkedy D, Leal JF, Shifman O, Moas M, Buschmann T, Ronai Z, Shiloh Y, Kastan MB, Katzir E, Oren M (2001) ATM-dependent phosphorylation of Mdm2 on serine 395: role in p53 activation by DNA damage. Genes Dev 15:1067–1077

    PubMed  CAS  Google Scholar 

  117. Meijer L, Arion D, Golsteyn R, Pines J, Brizuela L, Hunt T, Beach D (1989) Cyclin is a component of the sea urchin egg M-phase specific histone H1 kinase. EMBO J 8:2275–2282

    PubMed  CAS  Google Scholar 

  118. 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 413:311–316

    PubMed  CAS  Google Scholar 

  119. Momand J, Zambetti GP, Olson DC, George D, Levine AJ (1992) The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell 69:1237–1245

    PubMed  CAS  Google Scholar 

  120. Momand J, Wu HH, Dasgupta G (2000) MDM2-master regulator of the p53 tumor suppressor protein. Gene 242:15–29

    PubMed  CAS  Google Scholar 

  121. Morris MC, Kaiser P, Rudyak S, Baskerville C, Watson MH, Reed SI (2003) Cks1-dependent proteasome recruitment and activation of CDC20 transcription in budding yeast. Nature 423:1009–1013

    PubMed  CAS  Google Scholar 

  122. 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 USA 101:7937–7942

    PubMed  CAS  Google Scholar 

  123. Murray AW, Solomon MJ, Kirschner MW (1989) The role of cyclin synthesis and degradation in the control of maturation promoting factor activity. Nature 339:280–286

    PubMed  CAS  Google Scholar 

  124. Nakayama K, Nagahama H, Minamishima YA, Matsumoto M, Nakamichi I, Kitagawa K, Shirane M, Tsunematsu R, Tsukiyama T, Ishida N, Kitagawa M, Nakayama K, Hatakeyama S (2000) Targeted disruption of Skp2 results in accumulation of cyclin E and p27Kip1, polyploidy and centrosome overduplication. EMBO J 19:2069–2081

    PubMed  CAS  Google Scholar 

  125. Nash P, Tang X, Orlicky S, Chen Q, Gertler FB, Mendenhall MD, Sicheri F, Pawson T, Tyers M (2001) Multisite phosphorylation of a CDK inhibitor sets a threshold for the onset of DNA replication. Nature 414:514–521

    PubMed  CAS  Google Scholar 

  126. Nilsson JA, Cleveland JL (2003) Myc pathways provoking cell suicide and cancer. Oncogene 22:9007–9021

    PubMed  CAS  Google Scholar 

  127. Nugroho TT, Mendenhall MD (1994) An inhibitor of yeast cyclin-dependent protein kinase plays an important role in ensuring the genomic integrity of daughter cells. Mol Cell Biol 14:3320–3328

    PubMed  CAS  Google Scholar 

  128. Oberg C, Li J, Pauley A, Wolf E, Gurney M, Lendahl U (2001) The Notch intracellular domain is ubiquitinated and negatively regulated by the mammalian Sel-10 homolog. J Biol Chem 276:35847–35853

    PubMed  CAS  Google Scholar 

  129. 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 3:535–541

    PubMed  CAS  Google Scholar 

  130. Oliner JD, Pietenpol JA, Thiagalingam S, Gyuris J, Kinzler KW, Vogelstein B (1993) Oncoprotein MDM2 conceals the activation domain of tumour suppressor p53. Nature 362:857–860

    PubMed  CAS  Google Scholar 

  131. Oren M (1999) Regulation of the p53 tumor suppressor protein. J Biol Chem 274:36031–36034

    PubMed  CAS  Google Scholar 

  132. Orian A, Gonen H, Bercovich B, Fajerman I, Eytan E, Israel A, Mercurio F, Iwai K, Schwartz AL, Ciechanover A (2000) SCFβ-TrCP ubiquitin ligase-mediated processing of NF-kappaB p105 requires phosphorylation of its C-terminus by IkappaB kinase. EMBO J 19:2580–2591

    PubMed  CAS  Google Scholar 

  133. Orlicky S, Tang X, Willems A, Tyers M, Sicheri F (2003) Structural basis for phosphodependent substrate selection and orientation by the SCFCdc4 ubiquitin ligase. Cell 112:243–256

    PubMed  CAS  Google Scholar 

  134. Patton EE, Peyraud C, Rouillon A, Surdin-Kerjan Y, Tyers M, Thomas D (2000) SCFMet30-mediated control of the transcriptional activator Met4 is required for the G1–S transition. EMBO J 19:1613–1624

    PubMed  CAS  Google Scholar 

  135. Patton EE, Willems AR, Sa D, Kuras L, Thomas D, Craig KL, Tyers M (1998) Cdc53 is a scaffold protein for multiple Cdc34/Skp1/F-box protein complexes that regulate cell division and methionine biosynthesis in yeast. Genes Dev 12:692–705

    PubMed  CAS  Google Scholar 

  136. Peter M, Castro A, Lorca T, Le Peuch C, Magnaghi-Jaulin L, Doree M, Labbe JC (2001) The APC is dispensable for first meiotic anaphase in Xenopus oocytes. Nat Cell Biol 3:83–87

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  138. Pfleger CM, Lee E, Kirschner MW (2001) Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex. Genes Dev 15:2396–2407

    PubMed  CAS  Google Scholar 

  139. Pickart CM, Cohen RE (2004) Proteasomes and their kin: proteases in the machine age. Nat Rev Mol Cell Biol 5:177–187

    PubMed  CAS  Google Scholar 

  140. Pines J, Hunter T (1990) Human cyclin A is adenovirus E1A-associated protein p60 and behaves differently from cyclin B. Nature 346:760–763

    PubMed  CAS  Google Scholar 

  141. 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 8:750–760

    PubMed  CAS  Google Scholar 

  142. Prives C, Hall PA (1999) The p53 pathway. J Pathol 187:112–126

    PubMed  CAS  Google Scholar 

  143. Rajagopalan H, Jallepalli PV, Rago C, Velculescu VE, Kinzler KW, Vogelstein B, Lengauer C (2004) Inactivation of hCDC4 can cause chromosomal instability. Nature 428:77–81

    PubMed  CAS  Google Scholar 

  144. Rape M, Kirschner MW (2004) Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry. Nature 432:588–595

    PubMed  CAS  Google Scholar 

  145. Reimann JD, Freed E, Hsu JY, Kramer ER, Peters JM, Jackson PK (2001a) Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell 105:645–655

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  147. Russell ID, Grancell AS, Sorger PK (1999) The unstable F-box protein p58-Ctf13 forms the structural core of the CBF3 kinetochore complex. J Cell Biol 145:933–950

    PubMed  CAS  Google Scholar 

  148. Salah SM, Nasmyth K (2000) Destruction of the securin Pds1p occurs at the onset of anaphase during both meiotic divisions in yeast. Chromosoma 109:27–34

    PubMed  CAS  Google Scholar 

  149. Sanchez Y, Bachant J, Wang H, Hu F, Liu D, Tetzlaff M, Elledge SJ (1999) Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science 286:1166–1171

    PubMed  CAS  Google Scholar 

  150. Schulman BA, Carrano AC, Jeffrey PD, Bowen Z, Kinnucan ER, Finnin MS, Elledge SJ, Harper JW, Pagano M, Pavletich NP (2000) Insights into SCF ubiquitin ligases from the structure of the Skp1–Skp2 complex. Nature 408:381–386

    PubMed  CAS  Google Scholar 

  151. Schwab M, Lutum AS, Seufert W (1997) Yeast Hct1 is a regulator of Clb2 cyclin proteolysis. Cell 90:683–693

    PubMed  CAS  Google Scholar 

  152. Schwab M, Neutzner M, Mocker D, Seufert W (2001) Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC. EMBO J 20:5165–5175

    PubMed  CAS  Google Scholar 

  153. Schwob E, Bohm T, Mendenhall MD, Nasmyth K (1994) The B-type cyclin kinase inhibitor p40SIC1 controls the G1 to S transition in S. cerevisiae. Cell 79:233–244

    PubMed  CAS  Google Scholar 

  154. Seol JH, Feldman RM, Zachariae W, Shevchenko A, Correll CC, Lyapina S, Chi Y, Galova M, Claypool J, Sandmeyer S, Nasmyth K, 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 13:1614–1626

    PubMed  CAS  Google Scholar 

  155. Shirane M, Hatakeyama S, Hattori K, Nakayama K (1999) Common pathway for the ubiquitination of IkappaBalpha, IkappaBbeta, and IkappaBepsilon mediated by the F-box protein FWD1. J Biol Chem 274:28169–28174

    PubMed  CAS  Google Scholar 

  156. Shirayama M, Toth A, Galova M, Nasmyth K (1999) APCCdc20 promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5. Nature 402:203–207

    PubMed  CAS  Google Scholar 

  157. Sikorski RS, Boguski MS, Goebl M, Hieter P (1990) A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis. Cell 60:307–317

    PubMed  CAS  Google Scholar 

  158. Sitry D, Seeliger MA, Ko TK, Ganoth D, Breward SE, Itzhaki LS, Pagano M, Hershko A (2002) Three different binding sites of Cks1 are required for p27-ubiquitin ligation. J Biol Chem 277:42233–42240

    PubMed  CAS  Google Scholar 

  159. 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 91:209–219

    PubMed  CAS  Google Scholar 

  160. Skowyra D, Koepp DM, Kamura T, Conrad MN, Conaway RC, Conaway JW, Elledge SJ, Harper JW (1999) Reconstitution of G1 cyclin ubiquitination with complexes containing SCFGrr1 and Rbx1. Science 284:662–665

    PubMed  CAS  Google Scholar 

  161. Sorensen CS, Lukas C, Kramer ER, Peters JM, Bartek J, Lukas J (2001) A conserved cyclin-binding domain determines functional interplay between anaphase-promoting complex–Cdh1 and cyclin A–Cdk2 during cell cycle progression. Mol Cell Biol 21:3692–3703

    PubMed  CAS  Google Scholar 

  162. Spruck CH, Won KA, Reed SI (1999) Deregulated cyclin E induces chromosome instability. Nature 401:297–300

    PubMed  CAS  Google Scholar 

  163. Spruck C, Strohmaier H, Watson M, Smith AP, Ryan A, Krek TW, Reed SI (2001) A CDK-independent function of mammalian Cks1: targeting of SCFSkp2 to the CDK inhibitor p27Kip1. Mol Cell 7:639–650

    PubMed  CAS  Google Scholar 

  164. Spruck CH, Strohmaier H, Sangfelt O, Muller HM, Hubalek M, Muller-Holzner E, Marth C, Widschwendter M, Reed SI (2002) hCDC4 gene mutations in endometrial cancer. Cancer Res 62:4535–4539

    PubMed  CAS  Google Scholar 

  165. Stegmeier F, Visintin R, Amon A (2002) Separase, polo kinase, the kinetochore protein Slk19, and Spo12 function in a network that controls Cdc14 localization during early anaphase. Cell 108:207–220

    PubMed  CAS  Google Scholar 

  166. Stelter P, Ulrich HD (2003) Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation. Nature 425:188–191

    PubMed  CAS  Google Scholar 

  167. Stewart ZA, Pietenpol JA (2001) p53 Signaling and cell cycle checkpoints. Chem Res Toxicol 14:243–263

    PubMed  CAS  Google Scholar 

  168. 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 413:316–322

    PubMed  CAS  Google Scholar 

  169. 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 6:185–197

    PubMed  CAS  Google Scholar 

  170. Sullivan M, Lehane C, Uhlmann F (2001) Orchestrating anaphase and mitotic exit: separase cleavage and localization of Slk19. Nat Cell Biol 3:771–777

    PubMed  CAS  Google Scholar 

  171. Surana U, Amon A, Dowzer C, McGrew J, Byers B, Nasmyth K (1993) Destruction of the CDC28/CLB mitotic kinase is not required for the metaphase to anaphase transition in budding yeast. Embo J 12:1969–1978

    PubMed  CAS  Google Scholar 

  172. Sutterluty H, Chatelain E, Marti A, Wirbelauer C, Senften M, Muller U, Krek W (1999) p45SKP2 promotes p27Kip1 degradation and induces S phase in quiescent cells. Nat Cell Biol 1:207–214

    PubMed  CAS  Google Scholar 

  173. Suzuki H, Chiba T, Kobayashi M, Takeuchi M, Suzuki T, Ichiyama A, Ikenoue T, Omata M, Furuichi K, Tanaka K (1999) IkappaBalpha ubiquitination is catalyzed by an SCF-like complex containing Skp1, cullin-1, and two F-box/WD40-repeat proteins, betaTrCP1 and betaTrCP2. Biochem Biophys Res Commun 256:127–132

    PubMed  CAS  Google Scholar 

  174. Suzuki H, Chiba T, Suzuki T, Fujita T, Ikenoue T, Omata M, Furuichi K, Shikama H, Tanaka K (2000) Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds to IkappaBalpha for signal-dependent ubiquitination. J Biol Chem 275:2877–2884

    PubMed  CAS  Google Scholar 

  175. Swenson KI, Farrell KM, Ruderman JV (1986) The clam embryo protein cyclin A induces entry into M phase and the resumption of meiosis in Xenopus oocytes. Cell 47:861–870

    PubMed  CAS  Google Scholar 

  176. Taieb FE, Gross SD, Lewellyn AL, Maller JL (2001) Activation of the anaphase-promoting complex and degradation of cyclin B is not required for progression from Meiosis I to II in Xenopus oocytes. Curr Biol 11:508–513

    PubMed  CAS  Google Scholar 

  177. 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 IkappaB alpha. Mol Cell 3:527–533

    PubMed  CAS  Google Scholar 

  178. Tang Z, Bharadwaj R, Li B, Yu H (2001) Mad2-independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Dev Cell 1:227–237

    PubMed  CAS  Google Scholar 

  179. Tedesco D, Lukas J, Reed SI (2002) The pRb-related protein p130 is regulated by phosphorylation-dependent proteolysis via the protein–ubiquitin ligase SCFSkp2. Genes Dev 16:2946–2957

    PubMed  CAS  Google Scholar 

  180. Terret ME, Wassmann K, Waizenegger I, Maro B, Peters JM, Verlhac MH (2003) The meiosis I-to-meiosis II transition in mouse oocytes requires separase activity. Curr Biol 13:1797–1802

    PubMed  CAS  Google Scholar 

  181. Tetzlaff MT, Yu W, Li M, Zhang P, Finegold M, Mahon K, Harper JW, Schwartz RJ, Elledge SJ (2004) Defective cardiovascular development and elevated cyclin E and Notch proteins in mice lacking the Fbw7 F-box protein. Proc Natl Acad Sci USA 101:3338–3345

    PubMed  CAS  Google Scholar 

  182. Thomas D, Surdin-Kerjan Y (1997) Metabolism of sulfur amino acids in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 61:503–532

    PubMed  CAS  Google Scholar 

  183. Thornton BR, Toczyski DP (2003) Securin and B-cyclin/CDK are the only essential targets of the APC. Nat Cell Biol 5:1090–1094

    PubMed  CAS  Google Scholar 

  184. Tsunematsu R, Nakayama K, Oike Y, Nishiyama M, Ishida N, Hatakeyama S, Bessho Y, Kageyama R, Suda T, Nakayama KI (2004) Mouse Fbw7/Sel-10/Cdc4 is required for notch degradation during vascular development. J Biol Chem 279:9417–9423

    PubMed  CAS  Google Scholar 

  185. Tsvetkov LM, Yeh KH, Lee SJ, Sun H, Zhang H (1999) p27Kip1 ubiquitination and degradation is regulated by the SCFSkp2 complex through phosphorylated Thr187 in p27. Curr Biol 9:661–664

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  187. Verma R, Oania R, Graumann J, Deshaies RJ (2004) Multiubiquitin chain receptors define a layer of substrate selectivity in the ubiquitin–proteasome system. Cell 118:99–110

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  189. Visintin R, Craig K, Hwang ES, Prinz S, Tyers M, Amon A (1998) The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. Mol Cell 2:709–718

    PubMed  CAS  Google Scholar 

  190. Wahl GM, Carr AM (2001) The evolution of diverse biological responses to DNA damage: insights from yeast and p53. Nat Cell Biol 3:E277–286

    PubMed  CAS  Google Scholar 

  191. Waizenegger I, Gimenez-Abian JF, Wernic D, Peters JM (2002) Regulation of human separase by securin binding and autocleavage. Curr Biol 12:1368–1378

    PubMed  CAS  Google Scholar 

  192. Wang H, Liu D, Wang Y, Qin J, Elledge SJ (2001) Pds1 phosphorylation in response to DNA damage is essential for its DNA damage checkpoint function. Genes Dev 15:1361–1372

    PubMed  CAS  Google Scholar 

  193. Wang W, Ungermannova D, Chen L, Liu X (2003) A negatively charged amino acid in Skp2 is required for Skp2–Cks1 interaction and ubiquitination of p27Kip1. J Biol Chem 278:32390–32396

    PubMed  CAS  Google Scholar 

  194. Wang W, Ungermannova D, Chen L, Liu X (2004) Molecular and biochemical characterization of the Skp2–Cks1 binding interface. J Biol Chem 279:51362–51369

    PubMed  CAS  Google Scholar 

  195. Wasch R, Cross FR (2002) APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit. Nature 418:556–562

    PubMed  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  197. Waters JC, Chen RH, Murray AW, Salmon ED (1998) Localization of Mad2 to kinetochores depends on microtubule attachment, not tension. J Cell Biol 141:1181–1191

    PubMed  CAS  Google Scholar 

  198. Waters JC, Chen RH, Murray AW, Gorbsky GJ, Salmon ED, Nicklas RB (1999) Mad2 binding by phosphorylated kinetochores links error detection and checkpoint action in mitosis. Curr Biol 9:649–652

    PubMed  CAS  Google Scholar 

  199. 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 428:194–198

    PubMed  CAS  Google Scholar 

  200. Weinstein J (1997) Cell cycle-regulated expression, phosphorylation, and degradation of p55Cdc. A mammalian homolog of CDC20/Fizzy/slp1. J Biol Chem 272:28501–28511

    PubMed  CAS  Google Scholar 

  201. 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 12:381–392

    PubMed  CAS  Google Scholar 

  202. Welcker M, Orian A, Grim JA, Eisenman RN, Clurman BE (2004a) A nucleolar isoform of the Fbw7 ubiquitin ligase regulates c-Myc and cell size. Curr Biol 14:1852–1857

    PubMed  CAS  Google Scholar 

  203. Welcker M, Orian A, Jin J, Grim JA, Harper JW, Eisenman RN, Clurman BE (2004b) The Fbw7 tumor suppressor regulates glycogen synthase kinase 3 phosphorylation-dependent c-Myc protein degradation. Proc Natl Acad Sci USA 101:9085–9090

    PubMed  CAS  Google Scholar 

  204. 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 86:453–463

    PubMed  CAS  Google Scholar 

  205. Winston JT, Strack P, Beer-Romero P, Chu CY, Elledge SJ, Harper JW (1999) The SCFbeta–TRCP–ubiquitin ligase complex associates specifically with phosphorylated destruction motifs in IkappaBalpha and beta-catenin and stimulates IkappaBalpha ubiquitination in vitro. Genes Dev 13:270–283

    PubMed  CAS  Google Scholar 

  206. Wolf DA, McKeon F, Jackson PK (1999) F-box/WD-repeat proteins pop1p and Sud1p/Pop2p form complexes that bind and direct the proteolysis of cdc18p. Curr Biol 9:373–376

    PubMed  CAS  Google Scholar 

  207. Wu G, Xu G, Schulman BA, Jeffrey PD, Harper JW, Pavletich NP (2003) Structure of a beta-TrCP1-Skp1-beta-catenin complex: destruction motif binding and lysine specificity of the SCFβ-TrCP1 ubiquitin ligase. Mol Cell 11:1445–1456

    PubMed  CAS  Google Scholar 

  208. Wu G, Lyapina S, Das I, Li J, Gurney M, Pauley A, Chui I, Deshaies RJ, Kitajewski J (2001) SEL-10 is an inhibitor of notch signaling that targets notch for ubiquitin-mediated protein degradation. Mol Cell Biol 21:7403–7415

    PubMed  CAS  Google Scholar 

  209. Wu H, Lan Z, Li W, Wu S, Weinstein J, Sakamoto KM, Dai W (2000) p55CDC/hCDC20 is associated with BUBR1 and may be a downstream target of the spindle checkpoint kinase. Oncogene 19:4557–4562

    PubMed  CAS  Google Scholar 

  210. Wu X, Bayle JH, Olson D, Levine AJ (1993) The p53-mdm-2 autoregulatory feedback loop. Genes Dev 7:1126–1132

    PubMed  CAS  Google Scholar 

  211. Xiao Z, Chen Z, Gunasekera AH, Sowin TJ, Rosenberg SH, Fesik S, Zhang H (2003) Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents. J Biol Chem 278:21767–21773

    PubMed  CAS  Google Scholar 

  212. Xu K, Belunis C, Chu W, Weber D, Podlaski F, Huang KS, Reed SI, Vassilev LT (2003) Protein–protein interactions involved in the recognition of p27 by E3 ubiquitin ligase. Biochem J 371:957–964

    PubMed  CAS  Google Scholar 

  213. Yada M, Hatakeyama S, Kamura T, Nishiyama M, Tsunematsu R, Imaki H, Ishida N, Okumura F, Nakayama K, Nakayama KI (2004) Phosphorylation-dependent degradation of c-Myc is mediated by the F-box protein Fbw7. EMBO J 23:2116–2125

    PubMed  CAS  Google Scholar 

  214. Yamamoto A, Guacci V, Koshland D (1996a) Pds1p is required for faithful execution of anaphase in the yeast, Saccharomyces cerevisiae. J Cell Biol 133:85–97

    PubMed  CAS  Google Scholar 

  215. Yamamoto A, Guacci V, Koshland D (1996b) Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC and checkpoint pathway(s). J Cell Biol 133:99–110

    PubMed  CAS  Google Scholar 

  216. Yamano H, Gannon J, Mahbubani H, Hunt T (2004) Cell cycle-regulated recognition of the destruction box of cyclin B by the APC/C in Xenopus egg extracts. Mol Cell 13:137–147

    PubMed  CAS  Google Scholar 

  217. Yaron A, Gonen H, Alkalay I, Hatzubai A, Jung S, Beyth S, Mercurio F, Manning AM, Ciechanover A, Ben-Neriah Y (1997) Inhibition of NF-kappa-B cellular function via specific targeting of the I-kappa-B-ubiquitin ligase. EMBO J 16:6486–6494

    PubMed  CAS  Google Scholar 

  218. Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM, Andersen JS, Mann M, Mercurio F, Ben-Neriah Y (1998) Identification of the receptor component of the IkappaBalpha-ubiquitin ligase. Nature 396:590–594

    PubMed  CAS  Google Scholar 

  219. Yen JL, Su NY, Kaiser P (2005) The yeast ubiquitin ligase SCFMet30 regulates heavy metal response. Mol Biol Cell 16:1872–1882

    PubMed  CAS  Google Scholar 

  220. Yeong FM, Lim HH, Padmashree CG, Surana U (2000) Exit from mitosis in budding yeast: biphasic inactivation of the Cdc28-Clb2 mitotic kinase and the role of Cdc20. Mol Cell 5:501–511

    PubMed  CAS  Google Scholar 

  221. Yu VP, Baskerville C, Grunenfelder B, Reed SI (2005) A kinase-independent function of Cks1 and Cdk1 in regulation of transcription. Mol Cell 17:145–151

    PubMed  CAS  Google Scholar 

  222. Zachariae W, Nasmyth K (1996) TPR proteins required for anaphase progression mediate ubiquitination of mitotic B-type cyclins in yeast. Mol Biol Cell 7:791–801

    PubMed  CAS  Google Scholar 

  223. Zachariae W, Shin TH, Galova M, Obermaier B, Nasmyth K (1996) Identification of subunits of the anaphase-promoting complex of Saccharomyces cerevisiae. Science 274:1201–1204

    PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  225. Zachariae W, Shevchenko A, Andrews PD, Ciosk R, Galova M, Stark MJ, Mann M, Nasmyth K (1998b) Mass spectrometric analysis of the anaphase-promoting complex from yeast: identification of a subunit related to cullins. Science 279:1216–1219

    PubMed  CAS  Google Scholar 

  226. Zachariae W, Shin TH, Galova M, Obermaier B, Nasmyth K (1996) Identification of subunits of the anaphase-promoting complex of Saccharomyces cerevisiae. Science 274:1201–1204

    PubMed  CAS  Google Scholar 

  227. Zhao H, Watkins JL, Piwnica-Worms H (2002) Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci USA 99:14795–14800

    PubMed  CAS  Google Scholar 

  228. Zheng N, Schulman BA, Song L, Miller JJ, Jeffrey PD, Wang P, Chu C, Koepp DM, Elledge SJ, Pagano M, Conaway RC, Conaway JW, Harper JW, Pavletich NP (2002) Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature 416:703–709

    PubMed  CAS  Google Scholar 

  229. Zhu G, Spellman PT, Volpe T, Brown PO, Botstein D, Davis TN, Futcher B (2000) Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth. Nature 406:90–94

    PubMed  CAS  Google Scholar 

  230. Zou H, McGarry TJ, Bernal T, Kirschner MW (1999) Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 285:418–422

    PubMed  CAS  Google Scholar 

  231. Zur A, Brandeis M (2001) Securin degradation is mediated by fzy and fzr, and is required for complete chromatid separation but not for cytokinesis. EMBO J 20:792–801

    PubMed  CAS  Google Scholar 

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Correspondence to Steven I. Reed .

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Philipp Kaldis

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Reed, S.I. The ubiquitin-proteasome pathway in cell cycle control. In: Kaldis, P. (eds) Cell Cycle Regulation. Results and Problems in Cell Differentiation, vol 42. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b136681

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