Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The emerging role of APC/CCdh1 in controlling differentiation, genomic stability and tumor suppression

Abstract

Deregulation of the G1/G0 phase of the cell cycle can lead to cancer. During G1, most cells commit alternatively to DNA replication and division, or to cell-cycle exit and differentiation. The anaphase-promoting complex or cyclosome (APC/C) activated by Cdh1 coordinately eliminates positive cell-cycle regulators as well as inhibitors of differentiation, thereby coupling cell-cycle exit and differentiation. Misregulation of Cdh1 thus has the potential to promote both cell-cycle re-entry and either perturbed differentiation or dedifferentiation. In addition, APC/CCdh1 is required to maintain genomic stability. As a result, loss of Cdh1 can contribute to tumorigenesis in the form of proliferation of poorly differentiated and genetically unstable cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  • Adams J . (2004). The proteasome: a suitable antineoplastic target. Nat Rev Cancer 4: 349–360.

    Article  CAS  PubMed  Google Scholar 

  • Anand S, Penrhyn-Lowe S, Venkitaraman AR . (2003). AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell 3: 51–62.

    Article  CAS  PubMed  Google Scholar 

  • Araki M, Wharton RP, Tang Z, Yu H, Asano M . (2003). Degradation of origin recognition complex large subunit by the anaphase-promoting complex in Drosophila. EMBO J 22: 6115–6126.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Archambault V, Glover DM . (2009). Polo-like kinases: conservation and divergence in their functions and regulation. Nat Rev Mol Cell Biol 10: 265–275.

    CAS  PubMed  Google Scholar 

  • Barr AR, Gergely F . (2007). Aurora-A: the maker and breaker of spindle poles. J Cell Sci 120: 2987–2996.

    CAS  PubMed  Google Scholar 

  • 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: 190–193.

    Article  CAS  PubMed  Google Scholar 

  • 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: 256–267.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Benmaamar R, Pagano M . (2005). Involvement of the SCF complex in the control of Cdh1 degradation in S-phase. Cell Cycle 4: 1230–1232.

    CAS  PubMed  Google Scholar 

  • Binne UK, Classon MK, Dick FA, Wei W, Rape M, Kaelin Jr WG et al. (2007). Retinoblastoma protein and anaphase-promoting complex physically interact and functionally cooperate during cell-cycle exit. Nat Cell Biol 9: 225–232.

    CAS  PubMed  Google Scholar 

  • Bloom J, Cross FR . (2007). Multiple levels of cyclin specificity in cell-cycle control. Nat Rev Mol Cell Biol 8: 149–160.

    CAS  PubMed  Google Scholar 

  • Carroll CW, Morgan DO . (2002). The Doc1 subunit is a processivity factor for the anaphase-promoting complex. Nat Cell Biol 4: 880–887.

    CAS  PubMed  Google Scholar 

  • Carter SL, Eklund AC, Kohane IS, Harris LN, Szallasi Z . (2006). A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet 38: 1043–1048.

    CAS  PubMed  Google Scholar 

  • Castro A, Vigneron S, Bernis C, Labbe JC, Lorca T . (2003). Xkid is degraded in a D-box, KEN-box, and A-box-independent pathway. Mol Cell Biol 23: 4126–4138.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Castro A, Vigneron S, Bernis C, Labbe JC, Prigent C, Lorca T . (2002). The D-Box-activating domain (DAD) is a new proteolysis signal that stimulates the silent D-Box sequence of Aurora-A. EMBO Rep 3: 1209–1214.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chaudhary J, Sadler-Riggleman I, Ague JM, Skinner MK . (2005). The helix-loop-helix inhibitor of differentiation (ID) proteins induce post-mitotic terminally differentiated Sertoli cells to re-enter the cell cycle and proliferate. Biol Reprod 72: 1205–1217.

    CAS  PubMed  Google Scholar 

  • Crasta K, Huang P, Morgan G, Winey M, Surana U . (2006). Cdk1 regulates centrosome separation by restraining proteolysis of microtubule-associated proteins. EMBO J 25: 2551–2563.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Crasta K, Lim HH, Giddings Jr TH, Winey M, Surana U . (2008). Inactivation of Cdh1 by synergistic action of Cdk1 and polo kinase is necessary for proper assembly of the mitotic spindle. Nat Cell Biol 10: 665–675.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cross FR . (2003). Two redundant oscillatory mechanisms in the yeast cell cycle. Dev Cell 4: 741–752.

    CAS  PubMed  Google Scholar 

  • Cuende J, Moreno S, Bolanos JP, Almeida A . (2008). Retinoic acid downregulates Rae1 leading to APC (Cdh1) activation and neuroblastoma SH-SY5Y differentiation. Oncogene 27: 3339–3344.

    CAS  PubMed  Google Scholar 

  • Diffley JF . (2004). Regulation of early events in chromosome replication. Curr Biol 14: R778–R786.

    CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Engelbert D, Schnerch D, Baumgarten A, Wäsch R . (2008). The ubiquitin ligase APC(Cdh1) is required to maintain genome integrity in primary human cells. Oncogene 27: 907–917.

    CAS  PubMed  Google Scholar 

  • 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: 437–446.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrell Jr JE . (2002). Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 14: 140–148.

    CAS  PubMed  Google Scholar 

  • Floyd S, Pines J, Lindon C . (2008). APC/C Cdh1 targets aurora kinase to control reorganization of the mitotic spindle at anaphase. Curr Biol 18: 1649–1658.

    CAS  PubMed  Google Scholar 

  • Fujita T, Liu W, Doihara H, Date H, Wan Y . (2008a). Dissection of the APCCdh1-Skp2 cascade in breast cancer. Clin Cancer Res 14: 1966–1975.

    CAS  PubMed  Google Scholar 

  • 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: 217–228.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Garcia-Higuera I, Manchado E, Dubus P, Canamero M, Mendez J, Moreno S et al. (2008). Genomic stability and tumour suppression by the APC/C cofactor Cdh1. Nat Cell Biol 10: 802–811.

    PubMed  Google Scholar 

  • Gieffers C, Peters BH, Kramer ER, Dotti CG, Peters JM . (1999). Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons. Proc Natl Acad Sci USA 96: 11317–11322.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Hayes MJ, Kimata Y, Wattam SL, Lindon C, Mao G, Yamano H et al. (2006). Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with the APC/C. Nat Cell Biol 8: 607–614.

    CAS  PubMed  Google Scholar 

  • Hildebrandt ER, Hoyt MA . (2001). Cell cycle-dependent degradation of the Saccharomyces cerevisiae spindle motor Cin8p requires APC(Cdh1) and a bipartite destruction sequence. Mol Biol Cell 12: 3402–3416.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu JY, Reimann JD, Sorensen CS, Lukas J, Jackson PK . (2002). E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1). Nat Cell Biol 4: 358–366.

    CAS  PubMed  Google Scholar 

  • Jacobs H, Richter D, Venkatesh T, Lehner C . (2002). Completion of mitosis requires neither fzr/rap nor fzr2, a male germline-specific Drosophila Cdh1 homolog. Curr Biol 12: 1435–1441.

    CAS  PubMed  Google Scholar 

  • Jaquenoud M, van Drogen F, Peter M . (2002). Cell cycle-dependent nuclear export of Cdh1p may contribute to the inactivation of APC/C(Cdh1). EMBO J 21: 6515–6526.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ji M, Li H, Suh HC, Klarmann KD, Yokota Y, Keller JR . (2008). Id2 intrinsically regulates lymphoid and erythroid development via interaction with different target proteins. Blood 112: 1068–1077.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Juang YL, Huang J, Peters JM, McLaughlin ME, Tai CY, Pellman D . (1997). APC-mediated proteolysis of Ase1 and the morphogenesis of the mitotic spindle. Science 275: 1311–1314.

    CAS  PubMed  Google Scholar 

  • Keppler A, Gendreizig S, Gronemeyer T, Pick H, Vogel H, Johnsson K . (2003). A general method for the covalent labeling of fusion proteins with small molecules in vivo. Nat Biotechnol 21: 86–89.

    CAS  PubMed  Google Scholar 

  • Konishi Y, Stegmuller J, Matsuda T, Bonni S, Bonni A . (2004). Cdh1-APC controls axonal growth and patterning in the mammalian brain. Science 303: 1026–1030.

    CAS  PubMed  Google Scholar 

  • Kramer E, Scheuringer N, Podtelejnikov AV, Mann M, Peters J . (2000). Mitotic regulation of the APC activator proteins CDC20 and CDH1. Mol Biol Cell 11: 1555–1569.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lapenna S, Giordano A . (2009). Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov 8: 547–566.

    CAS  PubMed  Google Scholar 

  • Lasorella A, Stegmuller J, Guardavaccaro D, Liu G, Carro MS, Rothschild G et al. (2006). Degradation of Id2 by the anaphase-promoting complex couples cell cycle exit and axonal growth. Nature 442: 471–474.

    CAS  PubMed  Google Scholar 

  • Lassar AB, Thayer MJ, Overell RW, Weintraub H . (1989). Transformation by activated ras or fos prevents myogenesis by inhibiting expression of MyoD1. Cell 58: 659–667.

    CAS  PubMed  Google Scholar 

  • Lehman NL, Tibshirani R, Hsu JY, Natkunam Y, Harris BT, West RB et al. (2007). Oncogenic regulators and substrates of the anaphase promoting complex/cyclosome are frequently overexpressed in malignant tumors. Am J Pathol 170: 1793–1805.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • Li M, Shin YH, Hou L, Huang X, Wei Z, Klann E et al. (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: 1083–1089.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li M, Zhang P . (2009). The function of APC/CCdh1 in cell cycle and beyond. Cell Div 4: 2.

    PubMed  PubMed Central  Google Scholar 

  • Li W, Wu G, Wan Y . (2007). The dual effects of Cdh1/APC in myogenesis. FASEB J 21: 3606–3617.

    CAS  PubMed  Google Scholar 

  • Lindon C, Pines J . (2004). Ordered proteolysis in anaphase inactivates Plk1 to contribute to proper mitotic exit in human cells. J Cell Biol 164: 233–241.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Listovsky T, Oren YS, Yudkovsky Y, Mahbubani HM, Weiss AM, Lebendiker M et al. (2004). Mammalian Cdh1/Fzr mediates its own degradation. EMBO J 23: 1619–1626.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu W, Wu G, Li W, Lobur D, Wan Y . (2007). Cdh1-anaphase-promoting complex targets Skp2 for destruction in transforming growth factor beta-induced growth inhibition. Mol Cell Biol 27: 2967–2979.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Lorca T, Castro A, Martinez AM, Vigneron S, Morin N, Sigrist S et al. (1998). Fizzy is required for activation of the APC/Cyclosome in Xenopus egg extracts. EMBO J 17: 3565–3575.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Lwin T, Hazlehurst LA, Dessureault S, Lai R, Bai W, Sotomayor E et al. (2007). Cell adhesion induces p27Kip1-associated cell-cycle arrest through down-regulation of the SCFSkp2 ubiquitin ligase pathway in mantle-cell and other non-Hodgkin B-cell lymphomas. Blood 110: 1631–1638.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Malumbres M, Barbacid M . (2009). Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 9: 153–166.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Meraldi P, Honda R, Nigg EA . (2002). Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53−/− cells. EMBO J 21: 483–492.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Passmore LA, McCormack EA, Au SW, Paul A, Willison KR, Harper JW et al. (2003). Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. EMBO J 22: 786–796.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Perk J, Iavarone A, Benezra R . (2005). Id family of helix-loop-helix proteins in cancer. Nat Rev Cancer 5: 603–614.

    CAS  PubMed  Google Scholar 

  • 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  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Rape M, Reddy SK, Kirschner MW . (2006). The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell 124: 89–103.

    CAS  PubMed  Google Scholar 

  • Reis A, Levasseur M, Chang HY, Elliott DJ, Jones KT . (2006). The CRY box: a second APCcdh1-dependent degron in mammalian cdc20. EMBO Rep 7: 1040–1045.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ross KE, Cohen-Fix O . (2003). The role of Cdh1p in maintaining genomic stability in budding yeast. Genetics 165: 489–503.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Rudner A, Murray A . (2000). Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex. J Cell Biol 149: 1377–1390.

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • Sigrist SJ, Lehner CF . (1997). Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles. Cell 90: 671–681.

    CAS  PubMed  Google Scholar 

  • Skotheim JM, Di Talia S, Siggia ED, Cross FR . (2008). Positive feedback of G1 cyclins ensures coherent cell cycle entry. Nature 454: 291–296.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB et al. (1998). Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 9: 3273–3297.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stegmüller J, Huynh MA, Yuan Z, Konishi Y, Bonni A . (2008). TGFbeta-Smad2 signaling regulates the Cdh1-APC/SnoN pathway of axonal morphogenesis. J Neurosci 28: 1961–1969.

    PubMed  PubMed Central  Google Scholar 

  • Stegmüller 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: 389–400.

    PubMed  Google Scholar 

  • Steigemann P, Wurzenberger C, Schmitz MH, Held M, Guizetti J, Maar S et al. (2009). Aurora B-mediated abscission checkpoint protects against tetraploidization. Cell 136: 473–484.

    PubMed  Google Scholar 

  • Stewart S, Fang G . (2005). Anaphase-promoting compley/cyclosome controls the stability of TPX2 during mitotic exit. Mol Cell Biol 25: 10516–10527.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Strebhardt K, Ullrich A . (2006). Targeting polo-like kinase 1 for cancer therapy. Nat Rev Cancer 6: 321–330.

    CAS  PubMed  Google Scholar 

  • Stroschein SL, Bonni S, Wrana JL, Luo K . (2001). Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN. Genes Dev 15: 2822–2836.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sudo T, Ota Y, Kotani S, Nakao M, Takami Y, Takeda S et al. (2001). Activation of Cdh1-dependent APC is required for G1 cell cycle arrest and DNA damage-induced G2 checkpoint in vertebrate cells. EMBO J 20: 6499–6508.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Suh HC, Leeanansaksiri W, Ji M, Klarmann KD, Renn K, Gooya J et al. (2008). Id1 immortalizes hematopoietic progenitors in vitro and promotes a myeloproliferative disease in vivo. Oncogene 27: 5612–5623.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sullivan M, Morgan DO . (2007). A novel destruction sequence targets the meiotic regulator Spo13 for anaphase-promoting complex-dependent degradation in anaphase I. J Biol Chem 282: 19710–19715.

    CAS  PubMed  Google Scholar 

  • Takahashi C, Ewen ME . (2006). Genetic interaction between Rb and N-ras: differentiation control and metastasis. Cancer Res 66: 9345–9348.

    CAS  PubMed  Google Scholar 

  • Taylor S, Peters JM . (2008). Polo and Aurora kinases: lessons derived from chemical biology. Curr Opin Cell Biol 20: 77–84.

    CAS  PubMed  Google Scholar 

  • Vaziri C, Saxena S, Jeon Y, Lee C, Murata K, Machida Y et al. (2003). A p53-dependent checkpoint pathway prevents rereplication. Mol Cell 11: 997–1008.

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Wan Y, Liu X, Kirschner MW . (2001). The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction. Mol Cell 8: 1027–1039.

    CAS  PubMed  Google Scholar 

  • 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: 259–263.

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • Wäsch R, Engelbert D . (2005). Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells. Oncogene 24: 1–10.

    PubMed  Google Scholar 

  • Wei W, Ayad NG, Wan Y, Zhang GJ, Kirschner MW, Kaelin Jr WG . (2004). Degradation of the SCF component Skp2 in cell-cycle phase G1 by the anaphase-promoting complex. Nature 428: 194–198.

    CAS  PubMed  Google Scholar 

  • Wirth KG, Ricci R, Gimenez-Abian JF, Taghybeeglu S, Kudo NR, Jochum W et al. (2004). Loss of the anaphase-promoting complex in quiescent cells causes unscheduled hepatocyte proliferation. Genes Dev 18: 88–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wu G, Glickstein S, Liu W, Fujita T, Li W, Yang Q et al. (2007). The anaphase-promoting complex coordinates initiation of lens differentiation. Mol Biol Cell 18: 1018–1029.

    CAS  PubMed  PubMed Central  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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.

    CAS  PubMed  Google Scholar 

  • 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: 1721–1724.

    CAS  PubMed  Google Scholar 

  • 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: 33516–33524.

    CAS  PubMed  Google Scholar 

  • Zhou Y, Ching YP, Chun AC, Jin DY . (2003). Nuclear localization of the cell cycle regulator CDH1 and its regulation by phosphorylation. J Biol Chem 278: 12530–12536.

    CAS  PubMed  Google Scholar 

  • Zielke N, Querings S, Rottig C, Lehner C, Sprenger F . (2008). The anaphase-promoting complex/cyclosome (APC/C) is required for rereplication control in endoreplication cycles. Genes Dev 22: 1690–1703.

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Andrea Schmidts for helping us with Figure 2 and Monika Engelhardt for critical reading of the paper. RW thanks Roland Mertelsmann for continuous support.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R Wäsch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wäsch, R., Robbins, J. & Cross, F. The emerging role of APC/CCdh1 in controlling differentiation, genomic stability and tumor suppression. Oncogene 29, 1–10 (2010). https://doi.org/10.1038/onc.2009.325

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/onc.2009.325

Keywords

This article is cited by

Search

Quick links