The anaphase-promoting complex: a key factor in the regulation of cell cycle

Events controlling cell division are governed by the degradation of different regulatory proteins by the ubiquitin-dependent pathway. In this pathway, the attachment of a polyubiquitin chain to a substrate by an ubiquitin-ligase targets this substrate for degradation by the 26S proteasome. Two different ubiquitin ligases play an important role in the cell cycle: the SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC). In this review, we describe the present knowledge about the APC. We pay particular attention to the latest results concerning APC structure, APC regulation and substrate recognition, and we discuss the implication of these findings in the understanding the APC function.

[1]  G. G. Stokes.  "J." , 1890, The New Yale Book of Quotations.

[2]  L. Hartwell,et al.  Genetic control of the cell-division cycle in yeast. I. Detection of mutants. , 1970, Proceedings of the National Academy of Sciences of the United States of America.

[3]  Andrew W. Murray,et al.  Cyclin synthesis drives the early embryonic cell cycle , 1989, Nature.

[4]  Mark S. Boguski,et al.  A repeating amino acid motif in CDC23 defines a family of proteins and a new relationship among genes required for mitosis and RNA synthesis , 1990, Cell.

[5]  A. Murray,et al.  Cyclin is degraded by the ubiquitin pathway , 1991, Nature.

[6]  E. Nigg,et al.  Cyclin B2 undergoes cell cycle-dependent nuclear translocation and, when expressed as a non-destructible mutant, causes mitotic arrest in HeLa cells , 1992, The Journal of cell biology.

[7]  Andrew W. Murray,et al.  Anaphase is initiated by proteolysis rather than by the inactivation of maturation-promoting factor , 1993, Cell.

[8]  A. Hershko,et al.  Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[9]  M. Kirschner,et al.  A 20s complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B , 1995, Cell.

[10]  Kim Nasmyth,et al.  Genes involved in sister chromatid separation are needed for b-type cyclin proteolysis in budding yeast , 1995, Cell.

[11]  V. Guacci,et al.  Pds1p is required for faithful execution of anaphase in the yeast, Saccharomyces cerevisiae , 1996, The Journal of cell biology.

[12]  Stephen J. Elledge,et al.  SKP1 Connects Cell Cycle Regulators to the Ubiquitin Proteolysis Machinery through a Novel Motif, the F-Box , 1996, Cell.

[13]  M. Kirschner,et al.  Identification of BIME as a Subunit of the Anaphase-Promoting Complex , 1996, Science.

[14]  Hiroshi Yamada,et al.  20S cyclosome complex formation and proteolytic activity inhibited by the cAMP/PKA pathway , 1996, Nature.

[15]  K Nasmyth,et al.  Identification of Subunits of the Anaphase-Promoting Complex of Saccharomyces cerevisiae , 1996, Science.

[16]  J. Peters,et al.  APC-Mediated Proteolysis of Ase1 and the Morphogenesis of the Mitotic Spindle , 1997, Science.

[17]  S. Prinz,et al.  CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. , 1997, Science.

[18]  Michael Schwab,et al.  Yeast Hct1 Is a Regulator of Clb2 Cyclin Proteolysis , 1997, Cell.

[19]  C. Lehner,et al.  Drosophila fizzy-related Down-Regulates Mitotic Cyclins and Is Required for Cell Proliferation Arrest and Entry into Endocycles , 1997, Cell.

[20]  J. R. Daum,et al.  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 , 1998, The Journal of cell biology.

[21]  A. Ciechanover,et al.  The ubiquitin system. , 1998, Annual review of biochemistry.

[22]  M. Kirschner,et al.  The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. , 1998, Genes & development.

[23]  M. Kirschner,et al.  Identification of a cullin homology region in a subunit of the anaphase-promoting complex. , 1998, Science.

[24]  K Nasmyth,et al.  Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex. , 1998, Science.

[25]  M. Kirschner,et al.  Geminin, an Inhibitor of DNA Replication, Is Degraded during Mitosis , 1998, Cell.

[26]  M. Kirschner,et al.  Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. , 1998, Molecular cell.

[27]  Kim Nasmyth,et al.  The Polo‐like kinase Cdc5p and the WD‐repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae , 1998, The EMBO journal.

[28]  Kim Nasmyth,et al.  An ESP1/PDS1 Complex Regulates Loss of Sister Chromatid Cohesion at the Metaphase to Anaphase Transition in Yeast , 1998, Cell.

[29]  Alexandre V. Podtelejnikov,et al.  Characterization of the DOC1/APC10 Subunit of the Yeast and the Human Anaphase-promoting Complex* , 1999, The Journal of Biological Chemistry.

[30]  Friedrich Lottspeich,et al.  Sister-chromatid separation at anaphase onset is promoted by cleavage of the cohesin subunit Scc1 , 1999, Nature.

[31]  Attila Tóth,et al.  APCCdc20 promotes exit from mitosis by destroying the anaphase inhibitor Pds1 and cyclin Clb5 , 1999, Nature.

[32]  A. Murray,et al.  The Xenopus Chromokinesin Xkid Is Essential for Metaphase Chromosome Alignment and Must Be Degraded to Allow Anaphase Chromosome Movement , 2000, Cell.

[33]  M. Mann,et al.  The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[34]  K. Nasmyth,et al.  Destruction of the securin Pds1p occurs at the onset of anaphase during both meiotic divisions in yeast , 2000, Chromosoma.

[35]  M. Yanagida,et al.  Cell cycle mechanisms of sister chromatid separation; Roles of Cut1/separin and Cut2/securin , 2000, Genes to cells : devoted to molecular & cellular mechanisms.

[36]  M. J. Mallory,et al.  Ama1p is a meiosis-specific regulator of the anaphase promoting complex/cyclosome in yeast. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[37]  J. Labbé,et al.  The polo-like kinase Plx1 prevents premature inactivation of the APCFizzy-dependent pathway in the early Xenopus cell cycle , 2000, Oncogene.

[38]  I. Vernos,et al.  Xkid, a Chromokinesin Required for Chromosome Alignment on the Metaphase Plate , 2000, Cell.

[39]  Kim Nasmyth,et al.  Cleavage of Cohesin by the CD Clan Protease Separin Triggers Anaphase in Yeast , 2000, Cell.

[40]  Andrew W. Murray,et al.  Phosphorylation by Cdc28 Activates the Cdc20-Dependent Activity of the Anaphase-Promoting Complex , 2000, The Journal of cell biology.

[41]  M. Kirschner,et al.  Inhibition of Cdh1-APC by the MAD2-related protein MAD2L2: a novel mechanism for regulating Cdh1. , 2001, Genes & development.

[42]  M. Kirschner,et al.  Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex. , 2001, Genes & development.

[43]  D. Compton,et al.  The chromokinesin Kid is necessary for chromosome arm orientation and oscillation, but not congression, on mitotic spindles , 2001, The Journal of cell biology.

[44]  M. Kirschner,et al.  Identification of multiple CDH1 homologues in vertebrates conferring different substrate specificities , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[45]  J. Peters,et al.  Emi1 Is a Mitotic Regulator that Interacts with Cdc20 and Inhibits the Anaphase Promoting Complex , 2001, Cell.

[46]  D. Roof,et al.  Degradation of the kinesin Kip1p at anaphase onset is mediated by the anaphase-promoting complex and Cdc20p , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[47]  J Deisenhofer,et al.  APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. , 2001, Molecular biology of the cell.

[48]  Hongtao Yu,et al.  Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. , 2001, Developmental cell.

[49]  C. Larsson,et al.  Characterisation of the human APC1, the largest subunit of the anaphase-promoting complex. , 2001, Gene.

[50]  Tim Hunt,et al.  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 , 2001, The Journal of cell biology.

[51]  Avram Hershko,et al.  The Cyclin-Ubiquitin Ligase Activity of Cyclosome/APC Is Jointly Activated by Protein Kinases Cdk1-Cyclin B and Plk* , 2002, The Journal of Biological Chemistry.

[52]  J. Labbé,et al.  APC/Fizzy‐Related targets Aurora‐A kinase for proteolysis , 2002, EMBO reports.

[53]  J. Labbé,et al.  The D‐Box‐activating domain (DAD) is a new proteolysis signal that stimulates the silent D‐Box sequence of Aurora‐A , 2002, EMBO reports.

[54]  Christoph H Borchers,et al.  Mnd2 and Swm1 Are Core Subunits of the Saccharomyces cerevisiae Anaphase-promoting Complex* , 2003, The Journal of Biological Chemistry.

[55]  S. Gygi,et al.  Tome-1, a Trigger of Mitotic Entry, Is Degraded during G1 via the APC , 2003, Cell.

[56]  A. Castro,et al.  Bovine Papillomavirus Replicative Helicase E1 Is a Target of the Ubiquitin Ligase APC , 2004, Journal of Virology.

[57]  Rebecca A. Ihrie,et al.  Perp-etrating p53-Dependent Apoptosis , 2004, Cell cycle.