The anaphase-promoting complex: proteolysis in mitosis and beyond.

Key events in mitosis such as sister chromatid separation and subsequent inactivation of cyclin-dependent kinase 1 are regulated by ubiquitin-dependent proteolysis. These events are mediated by the anaphase-promoting complex (APC), a cell cycle-regulated ubiquitin ligase that assembles multiubiquitin chains on regulatory proteins such as securin and cyclins and thereby targets them for destruction by the 26S proteasome.

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

[2]  J. Peters,et al.  Three-dimensional structure of the anaphase-promoting complex. , 2001, Molecular cell.

[3]  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.

[4]  A. Murray,et al.  A novel yeast screen for mitotic arrest mutants identifies DOC1, a new gene involved in cyclin proteolysis. , 1997, Molecular biology of the cell.

[5]  Angelika Amon,et al.  Separase, Polo Kinase, the Kinetochore Protein Slk19, and Spo12 Function in a Network that Controls Cdc14 Localization during Early Anaphase , 2002, Cell.

[6]  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.

[7]  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.

[8]  J. Peters,et al.  Ubiquitin and the Biology of the Cell , 1998, Springer US.

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

[10]  Budding yeast Cdc20 , 1998 .

[11]  S. Artavanis-Tsakonas,et al.  The Drosophila cell cycle gene fizzy is required for normal degradation of cyclins A and B during mitosis and has homology to the CDC20 gene of Saccharomyces cerevisiae , 1995, The Journal of cell biology.

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

[13]  M. Hoyt,et al.  Cell cycle-dependent degradation of the Saccharomyces cerevisiae spindle motor Cin8p requires APC(Cdh1) and a bipartite destruction sequence. , 2001, Molecular biology of the cell.

[14]  R. Bernards,et al.  Distinct Initiation and Maintenance Mechanisms Cooperate to Induce G1 Cell Cycle Arrest in Response to DNA Damage , 2000, Cell.

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

[16]  J. Peters,et al.  Cell Cycle Control by Ubiquitin-Dependent Proteolysis , 1998 .

[17]  K. Helin,et al.  Mad2 binding to Mad1 and Cdc20, rather than oligomerization, is required for the spindle checkpoint , 2001, The EMBO journal.

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

[19]  Leslie Wilson,et al.  Mammalian mad2 and bub1/bubR1 recognize distinct spindle-attachment and kinetochore-tension checkpoints , 2001, Proceedings of the National Academy of Sciences of the United States of America.

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

[21]  O. Cohen-Fix,et al.  The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner , 2001, Current Biology.

[22]  J. Peters,et al.  A Conserved Cyclin-Binding Domain Determines Functional Interplay between Anaphase-Promoting Complex–Cdh1 and Cyclin A-Cdk2 during Cell Cycle Progression , 2001, Molecular and Cellular Biology.

[23]  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.

[24]  J. Wrana,et al.  Smad3 recruits the anaphase-promoting complex for ubiquitination and degradation of SnoN. , 2001, Genes & development.

[25]  A. Amon The spindle checkpoint. , 1999, Current opinion in genetics & development.

[26]  G. Chan,et al.  Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2 , 2001, The Journal of cell biology.

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

[28]  K. Nasmyth,et al.  The anaphase-promoting complex is required in G1 arrested yeast cells to inhibit B-type cyclin accumulation and to prevent uncontrolled entry into S-phase. , 1997, Journal of cell science.

[29]  Hongtao Yu,et al.  The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. , 2002, Molecular cell.

[30]  R. Deshaies SCF and Cullin/Ring H2-based ubiquitin ligases. , 1999, Annual review of cell and developmental biology.

[31]  J. Peters,et al.  Subunits and substrates of the anaphase-promoting complex. , 1999, Experimental cell research.

[32]  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.

[33]  Angelika Amon,et al.  The regulation of Cdc20 proteolysis reveals a role for the APC components Cdc23 and Cdc27 during S phase and early mitosis , 1998, Current Biology.

[34]  Jiri Bartek,et al.  Accumulation of cyclin B1 requires E2F and cyclin-A-dependent rearrangement of the anaphase-promoting complex , 1999, Nature.

[35]  Kim Nasmyth,et al.  Closing the cell cycle circle in yeast: G2 cyclin proteolysis initiated at mitosis persists until the activation of G1 cyclins in the next cycle , 1994, Cell.

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

[37]  M. Kirschner,et al.  The KEN box: an APC recognition signal distinct from the D box targeted by Cdh1. , 2000, Genes & development.

[38]  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.

[39]  C. Rieder,et al.  Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle , 1994, The Journal of cell biology.

[40]  R. Nicklas,et al.  Mitotic forces control a cell-cycle checkpoint , 1995, Nature.

[41]  David O. Morgan,et al.  Regulation of the APC and the exit from mitosis , 1999, Nature Cell Biology.

[42]  P. Jackson,et al.  Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins. , 2001, Genes & development.

[43]  T. Maeda,et al.  Human p55(CDC)/Cdc20 associates with cyclin A and is phosphorylated by the cyclin A-Cdk2 complex. , 2000, Biochemical and biophysical research communications.

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

[45]  A. Amon,et al.  A Mechanism for Coupling Exit from Mitosis to Partitioning of the Nucleus , 2000, Cell.

[46]  K. Kitamura,et al.  Fission yeast Ste9, a homolog of Hct1/Cdh1 and Fizzy-related, is a novel negative regulator of cell cycle progression during G1-phase. , 1998, Molecular biology of the cell.

[47]  A. Hershko,et al.  Methylated ubiquitin inhibits cyclin degradation in clam embryo extracts. , 1991, The Journal of biological chemistry.

[48]  S. Elledge,et al.  Structure of the Cul1–Rbx1–Skp1–F boxSkp2 SCF ubiquitin ligase complex , 2002, Nature.

[49]  A. Murray,et al.  Budding yeast Cdc20: a target of the spindle checkpoint. , 1998, Science.

[50]  J. Diffley,et al.  CDK inactivation is the only essential function of the APC/C and the mitotic exit network proteins for origin resetting during mitosis. , 2000, Molecular cell.

[51]  Michael R. Speicher,et al.  Securin Is Required for Chromosomal Stability in Human Cells , 2001, Cell.

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

[53]  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.

[54]  M. Brandeis,et al.  Cdk1 is essential for mammalian cyclosome/APC regulation. , 2000, Experimental cell research.

[55]  J. Peters,et al.  Two Distinct Pathways Remove Mammalian Cohesin from Chromosome Arms in Prophase and from Centromeres in Anaphase , 2000, Cell.

[56]  M. Mann,et al.  Mitotic regulation of the APC activator proteins CDC20 and CDH1. , 2000, Molecular biology of the cell.

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

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

[59]  M. Kitagawa,et al.  Cell cycle-dependent expression of mammalian E2-C regulated by the anaphase-promoting complex/cyclosome. , 2000, Molecular biology of the cell.

[60]  K Nasmyth,et al.  Mass spectrometric analysis of the anaphase-promoting complex from yeast: identification of a subunit related to cullins. , 1998, Science.

[61]  Y. Protopopov,et al.  Phosphorylation of the cyclosome is required for its stimulation by Fizzy/cdc20. , 1999, Biochemical and biophysical research communications.

[62]  J. Peters,et al.  Expression of the CDH1-associated form of the anaphase-promoting complex in postmitotic neurons. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[63]  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.

[64]  M. Kirschner,et al.  Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation , 1996, Current Biology.

[65]  K. Nasmyth,et al.  Whose end is destruction: cell division and the anaphase-promoting complex. , 1999, Genes & development.

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

[67]  Anna Shevchenko,et al.  Exit from Mitosis Is Triggered by Tem1-Dependent Release of the Protein Phosphatase Cdc14 from Nucleolar RENT Complex , 1999, Cell.

[68]  M. Solomon,et al.  D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p. , 2001, Genes & development.

[69]  A. Amon,et al.  MEN and SIN: what's the difference? , 2001, Nature Reviews Molecular Cell Biology.

[70]  A. Fry,et al.  APC/C‐mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A‐type D‐box , 2001, The EMBO journal.

[71]  Stuart Tugendreich,et al.  CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition , 1995, Cell.

[72]  David Pellman,et al.  Activity of the APCCdh1 form of the anaphase-promoting complex persists until S phase and prevents the premature expression of Cdc20p , 2001, The Journal of cell biology.

[73]  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.

[74]  D. Barford,et al.  Implications for the ubiquitination reaction of the anaphase-promoting complex from the crystal structure of the Doc1/Apc10 subunit. , 2002, Journal of molecular biology.

[75]  I. Sumara,et al.  The dissociation of cohesin from chromosomes in prophase is regulated by Polo-like kinase. , 2002, Molecular cell.

[76]  T. Hirano,et al.  Identification of Xenopus SMC protein complexes required for sister chromatid cohesion. , 1998, Genes & development.

[77]  T. Toda,et al.  Apc10 and Ste9/Srw1, two regulators of the APC–cyclosome, as well as the CDK inhibitor Rum1 are required for G1 cell‐cycle arrest in fission yeast , 1998, The EMBO journal.

[78]  Andrew W. Murray,et al.  Association of Spindle Assembly Checkpoint Component XMAD2 with Unattached Kinetochores , 1996, Science.

[79]  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.

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

[81]  R. Benezra,et al.  Mad2 transiently associates with an APC/p55Cdc complex during mitosis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[82]  M. Nakao,et al.  Activation of Cdh1‐dependent APC is required for G1 cell cycle arrest and DNA damage‐induced G2 checkpoint in vertebrate cells , 2001, The EMBO journal.

[83]  P. Nurse,et al.  Fission yeast Fizzy‐related protein srw1p is a G1‐specific promoter of mitotic cyclin B degradation , 2000, The EMBO journal.

[84]  Hongtao Yu,et al.  Regulation of the Anaphase-promoting Complex by the Dual Specificity Phosphatase Human Cdc14a* , 2001, The Journal of Biological Chemistry.

[85]  T. Hunt,et al.  The proteolysis of mitotic cyclins in mammalian cells persists from the end of mitosis until the onset of S phase. , 1996, The EMBO journal.

[86]  T. Toda,et al.  Fission yeast TPR-family protein nuc2 is required for G1-arrest upon nitrogen starvation and is an inhibitor of septum formation. , 1995, Journal of cell science.

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

[88]  S. Moreno,et al.  APCste9/srw1 promotes degradation of mitotic cyclins in G1 and is inhibited by cdc2 phosphorylation , 2000, The EMBO journal.

[89]  A. Murray,et al.  Localization of Mad2 to Kinetochores Depends on Microtubule Attachment, Not Tension , 1998, The Journal of cell biology.

[90]  Eric T. Rosenthal,et al.  Cyclin: A protein specified by maternal mRNA in sea urchin eggs that is destroyed at each cleavage division , 1983, Cell.

[91]  G. Braus,et al.  Two different modes of cyclin Clb2 proteolysis during mitosis in Saccharomyces cerevisiae , 2000, FEBS letters.

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

[93]  F. M. Yeong,et al.  Exit from mitosis in budding yeast: biphasic inactivation of the Cdc28-Clb2 mitotic kinase and the role of Cdc20. , 2000, Molecular cell.

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

[95]  P. Hieter,et al.  The APC11 RING-H2 finger mediates E2-dependent ubiquitination. , 2000, Molecular biology of the cell.

[96]  V. Guacci,et al.  Pds1p, an inhibitor of anaphase in budding yeast, plays a critical role in the APC and checkpoint pathway(s) , 1996, The Journal of cell biology.

[97]  M. Kirschner,et al.  The anaphase-promoting complex mediates TGF-beta signaling by targeting SnoN for destruction. , 2001, Molecular cell.

[98]  T. T. Su Cell cycle: How, when and why cells get rid of cyclin A , 2001, Current Biology.

[99]  J. Pines,et al.  Temporal and spatial control of cyclin B1 destruction in metaphase , 1999, Nature Cell Biology.

[100]  S. Gygi,et al.  Dual Inhibition of Sister Chromatid Separation at Metaphase , 2001, Cell.

[101]  A. Murray,et al.  Lack of tension at kinetochores activates the spindle checkpoint in budding yeast , 2001, Current Biology.

[102]  S. Zipursky,et al.  Control of G1 in the developing Drosophila eye: rca1 regulates Cyclin A. , 1997, Genes & development.

[103]  J. Peters,et al.  Cohesin Cleavage by Separase Required for Anaphase and Cytokinesis in Human Cells , 2001, Science.

[104]  W. Seufert,et al.  Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC , 2001, The EMBO journal.

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

[106]  A. Hershko,et al.  The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. , 1995, Molecular biology of the cell.

[107]  David O. Morgan,et al.  Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14 , 1999, Current Biology.

[108]  J. Massagué,et al.  TGFβ Signaling in Growth Control, Cancer, and Heritable Disorders , 2000, Cell.

[109]  C. Lehner,et al.  Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts , 1998, The EMBO journal.

[110]  J. Pines,et al.  Cyclin a Is Destroyed in Prometaphase and Can Delay Chromosome Alignment and Anaphase , 2001, The Journal of cell biology.

[111]  S. Fang,et al.  RING fingers mediate ubiquitin-conjugating enzyme (E2)-dependent ubiquitination. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

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

[113]  M. Tyers,et al.  The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. , 1998, Molecular cell.

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

[115]  R. Huber,et al.  Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex , 2001, Nature Structural Biology.

[116]  C. Lehner,et al.  Exit from mitosis is regulated by Drosophila fizzy and the sequential destruction of cyclins A, B and B3. , 1995, The EMBO journal.

[117]  F. Sprenger,et al.  Rca1 inhibits APC-Cdh1(Fzr) and is required to prevent cyclin degradation in G2. , 2002, Developmental cell.

[118]  K. Nasmyth THE GENOME : Joining , Resolving , and Separating Sister Chromatids During Mitosis and Meiosis , 2006 .