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Structure, function and mechanism of the anaphase promoting complex (APC/C)

  • David Barford (a1)
  • DOI:
  • Published online: 22 November 2010

The complex molecular events responsible for coordinating chromosome replication and segregation with cell division and growth are collectively known as the cell cycle. Progression through the cell cycle is orchestrated by the interplay between controlled protein synthesis and degradation and protein phosphorylation. Protein degradation is primarily regulated through the ubiquitin proteasome system, mediated by two related E3 protein ubiquitin ligases, the Skp1 cullin F-box (SCF) and the anaphase promoting complex (also known as the cyclosome) (APC/C). The APC/C is a multi-subunit cullin-RING E3 ubiquitin ligase that regulates progression through the mitotic phase of the cell cycle and controls entry into S phase by catalysing the ubiquitylation of cyclins and other cell cycle regulatory proteins. Selection of APC/C targets is controlled through recognition of short destruction motifs, predominantly the D-box and KEN-box. APC/C-mediated coordination of cell cycle progression is achieved through the temporal regulation of APC/C activity and substrate specificity, exerted through a combination of co-activator subunits, reversible phosphorylation and inhibitory proteins and complexes. The aim of this article is to discuss the APC/C from a structural and mechanistic perspective. Although an atomic structure of the APC/C is still lacking, a combination of genetic, biochemical, electron microscopy studies of intact APC/C and crystallographic analysis of individual subunits, together with analogies to evolutionarily related E3 ligases of the RING family, has provided deep insights into the molecular mechanisms of catalysis and substrate recognition, and structural organisation of the APC/C.

Corresponding author
*Author for correspondence: D. Barford, Section of Structural Biology, Institute of Cancer Research, Chester Beatty Laboratories, 237 Fulham Road, London, SW3 6JB, UK. Email:
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V. Amador , S. Ge , P. G. Santamaria , D. Guardavaccaro & M. Pagano (2007). APC/C(Cdc20) controls the ubiquitin-mediated degradation of p21 in prometaphase. Molecular Cell 27, 462473.

A. Aristarkhov , E. Eytan , A. Moghe , A. Admon , A. Hershko & J. V. Ruderman (1996). E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins. Proceedings of the National Academy of Sciences of the United States of America 93, 42944299.

S. W. Au , X. Leng , J. W. Harper & D. Barford (2002). Implications for the ubiquitination reaction of the anaphase-promoting complex from the crystal structure of the Doc1/Apc10 subunit. Journal of Molecular Biology 316, 955968.

N. G. Ayad , S. Rankin , M. Murakami , J. Jebanathirajah , S. Gygi & M. W. Kirschner (2003). Tome-1, a trigger of mitotic entry, is degraded during G1 via the APC. Cell 113, 101113.

J. A. Benanti , M. E. Matyskiela , D. O. Morgan & D. P. Toczyski (2009). Functionally distinct isoforms of Cik1 are differentially regulated by APC/C-mediated proteolysis. Molecular Cell 33, 581590.

E. Berdougo , M. V. Nachury , P. K. Jackson & P. V. Jallepalli (2008). The nucleolar phosphatase Cdc14B is dispensable for chromosome segregation and mitotic exit in human cells. Cell Cycle 7, 11841190.

V. M. Bolanos-Garcia , T. Kiyomitsu , S. D'ARCY , D. Y. Chirgadze , J. G. Grossmann , D. Matak-Vinkovic , A. R. Venkitaraman , M. Yanagida , C. V. Robinson & T. L. Blundell (2009). The crystal structure of the N-terminal region of BUB1 provides insight into the mechanism of BUB1 recruitment to kinetochores. Structure 17, 105116.

I. Braunstein , S. Miniowitz , Y. Moshe & A. Hershko (2007). Inhibitory factors associated with anaphase-promoting complex/cylosome in mitotic checkpoint. Proceedings of the National Academy of Sciences of the United States of America 104, 48704875.

J. L. Burton & M. J. Solomon (2001). D box and KEN box motifs in budding yeast Hsl1p are required for APC-mediated degradation and direct binding to Cdc20p and Cdh1p. Genes and Development 15, 23812395.

J. L. Burton & M. J. Solomon (2007). Mad3p, a pseudosubstrate inhibitor of APCCdc20 in the spindle assembly checkpoint. Genes and Development 21, 655667.

J. L. Burton , V. Tsakraklides & M. J. Solomon (2005). Assembly of an APC-Cdh1-substrate complex is stimulated by engagement of a destruction box. Molecular Cell 18, 533542.

A. Camasses , A. Bogdanova , A. Shevchenko & W. Zachariae (2003). The CCT chaperonin promotes activation of the anaphase-promoting complex through the generation of functional Cdc20. Molecular Cell 12, 87100.

A. D. Capili & C. D. Lima (2007). Taking it step by step: mechanistic insights from structural studies of ubiquitin/ubiquitin-like protein modification pathways. Current Opinion in Structural Biology 17, 726735.

C. W. Carroll , M. Enquist-Newman & D. O. Morgan (2005). The APC subunit Doc1 promotes recognition of the substrate destruction box. Current Biology 15, 1118.

C. W. Carroll & D. O. Morgan (2002). The Doc1 subunit is a processivity factor for the anaphase-promoting complex. Nature Cell Biology 4, 880887.

A. Castro , S. Vigneron , C. Bernis , J. C. Labbe & T. Lorca (2003). Xkid is degraded in a D-box, KEN-box, and A-box-independent pathway. Molecular and Cellular Biology 23, 41264138.

A. Castro , S. Vigneron , C. Bernis , J. C. Labbe , C. Prigent & T. Lorca (2002). The D-Box-activating domain (DAD) is a new proteolysis signal that stimulates the silent D-Box sequence of Aurora-A. EMBO Reports 3, 12091214.

V. Chau , J. W. Tobias , A. Bachmair , D. Marriott , D. J. Ecker , D. K. Gonda & A. Varshavsky (1989). A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science 243, 15761583.

E. Choi , J. M. Dial , D. E. Jeong & M. C. Hall (2008). Unique D box and KEN box sequences limit ubiquitination of Acm1 and promote pseudosubstrate inhibition of the anaphase-promoting complex. Journal of Biological Chemistry 283, 2370123710.

E. Chung & R. H. Chen (2003). Phosphorylation of Cdc20 is required for its inhibition by the spindle checkpoint. Nature Cell Biology 5, 748753.

R. Ciosk , W. Zachariae , C. Michaelis , A. Shevchenko , M. Mann & K. Nasmyth (1998). An ESP1/PDS1 complex regulates loss of sister chromatid cohesion at the metaphase to anaphase transition in yeast. Cell 93, 10671076.

O. Cohen-Fix , J. M. Peters , M. W. Kirschner & D. Koshland (1996). Anaphase initiation in Saccharomyces cerevisiae is controlled by the APC-dependent degradation of the anaphase inhibitor Pds1p. Genes and Development 10, 30813093.

I. A. Dawson , S. Roth & S. Artavanis-Tsakonas (1995). 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. Journal of Cell Biology 129, 725737.

N. Den Elzen & J. Pines (2001). Cyclin A is destroyed in prometaphase and can delay chromosome alignment and anaphase. Journal of Cell Biology 153, 121136.

R. J. Deshaies & C. A. Joazeiro (2009). RING domain E3 ubiquitin ligases. Annual Review of Biochemistry 78, 399434.

B. Di Fiore & J. Pines (2008). Defining the role of Emi1 in the DNA replication-segregation cycle. Chromosoma 117, 333338.

J. M. Dial , E. V. Petrotchenko & C. H. Borchers (2007). Inhibition of APCCdh1 activity by Cdh1/Acm1/Bmh1 ternary complex formation. Journal of Biological Chemistry 282, 52375248.

D. C. Dias , G. Dolios , R. Wang & Z. Q. Pan (2002). CUL7: A DOC domain-containing cullin selectively binds Skp1.Fbx29 to form an SCF-like complex. Proceedings of the National Academy of Sciences of the United States of America 99, 1660116606.

P. Dube , F. Herzog , C. Gieffers , B. Sander , D. Riedel , S. A. Muller , A. Engel , J. M. Peters & H. Stark (2005). Localization of the coactivator Cdh1 and the cullin subunit Apc2 in a cryo-electron microscopy model of vertebrate APC/C. Molecular Cell 20, 867879.

D. M. Duda , L. A. Borg , D. C. Scott , H. W. Hunt , M. Hammel & B. A. Schulman (2008). Structural insights into NEDD8 activation of cullin-RING ligases: conformational control of conjugation. Cell 134, 9951006.

A. G. Eldridge , A. V. Loktev , D. V. Hansen , E. W. Verschuren , J. D. Reimann & P. K. Jackson (2006). The evi5 oncogene regulates cyclin accumulation by stabilizing the anaphase-promoting complex inhibitor emi1. Cell 124, 367380.

M. Enquist-Newman , M. Sullivan & D. O. Morgan (2008). Modulation of the mitotic regulatory network by APC-dependent destruction of the Cdh1 inhibitor Acm1. Molecular Cell 30, 437446.

E. Eytan , I. Braunstein , D. Ganoth , A. Teichner , J. C. Hittle , T. J. Yen & A. Hershko (2008). Two different mitotic checkpoint inhibitors of the anaphase-promoting complex/cyclosome antagonize the action of the activator Cdc20. Proceedings of the National Academy of Sciences of the United States of America 105, 91819185.

E. Eytan , Y. Moshe , I. Braunstein & A. Hershko (2006). Roles of the anaphase-promoting complex/cyclosome and of its activator Cdc20 in functional substrate binding. Proceedings of the National Academy of Sciences of the United States of America 103, 20812086.

G. Fang , H. Yu & M. W. Kirschner (1998a). Direct binding of CDC20 protein family members activates the anaphase-promoting complex in mitosis and G1. Molecular Cell 2, 163171.

G. Fang , H. Yu & M. W. Kirschner (1998b). The checkpoint protein MAD2 and the mitotic regulator CDC20 form a ternary complex with the anaphase-promoting complex to control anaphase initiation. Genes and Development 12, 18711883.

D. J. Fitzgerald , C. Schaffitzel , P. Berger , R. Wellinger , C. Bieniossek , T. J. Richmond & I. Berger (2007). Multiprotein expression strategy for structural biology of eukaryotic complexes. Structure 15, 275279.

R. Fraschini , A. Beretta , L. Sironi , A. Musacchio , G. Lucchini & S. Piatti (2001). Bub3 interaction with Mad2, Mad3 and Cdc20 is mediated by WD40 repeats and does not require intact kinetochores. Embo Journal 20, 66486659.

A. M. Fry & H. Yamano (2008). Under arrest in mitosis: Cdc20 dies twice. Nature Cell Biology 10, 13851387.

H. Funabiki , H. Yamano , K. Kumada , K. Nagao , T. Hunt & M. Yanagida (1996). Cut2 proteolysis required for sister-chromatid seperation in fission yeast. Nature 381, 438441.

M. Funakoshi , R. J. Tomko Jr., H. Kobayashi & M. Hochstrasser (2009). Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle base. Cell 137, 887899.

M. J. Garnett , J. Mansfeld , C. Godwin , T. Matsusaka , J. Wu , P. Russell , J. Pines & A. R. Venkitaraman (2009). UBE2S elongates ubiquitin chains on APC/C substrates to promote mitotic exit. Nature Cell Biology 11, 13631369.

S. Gazdoiu , K. Yamoah , K. Wu , C. R. Escalante , I. Tappin , V. Bermudez , A. K. Aggarwal , J. Hurwitz & Z. Q. Pan (2005). Proximity-induced activation of human Cdc34 through heterologous dimerization. Proceedings of the National Academy of Sciences of the United States of America 102, 1505315058.

S. Geley , E. Kramer , C. Gieffers , J. Gannon , J. M. Peters & T. Hunt (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. Journal of Cell Biology 153, 137148.

M. Glotzer , A. W. Murray & M. W. Kirschner (1991). Cyclin is degraded by the ubiquitin pathway. Nature 349, 132138.

M. Gmachl , C. Gieffers , A. V. Podtelejnikov , M. Mann & J. M. Peters (2000). The RING-H2 finger protein APC11 and the E2 enzyme UBC4 are sufficient to ubiquitinate substrates of the anaphase-promoting complex. Proceedings of the National Academy of Sciences of the United States of America 97, 89738978.

A. Golan , Y. Yudkovsky & A. Hershko (2002). The cyclin-ubiquitin ligase activity of cyclosome/APC is jointly activated by protein kinases Cdk1-cyclin B and Plk. Journal of Biological Chemistry 277, 1555215557.

D. M. Gordon & D. M. Roof (2001). Degradation of the kinesin Kip1p at anaphase onset is mediated by the anaphase-promoting complex and Cdc20p. Proceedings of the National Academy of Sciences of the United States of America 98, 1251512520.

I. H. Gorr , D. Boos & O. Stemmann (2005). Mutual inhibition of separase and Cdk1 by two-step complex formation. Molecular Cell 19, 135141.

R. Grossberger , C. Gieffers , W. Zachariae , A. V. Podtelejnikov , A. Schleiffer , K. Nasmyth , M. Mann & J. M. Peters (1999). Characterization of the DOC1/APC10 subunit of the yeast and the human anaphase-promoting complex. Journal of Biological Chemistry 274, 1450014507.

R. Grosskortenhaus & F. Sprenger (2002). Rca1 inhibits APC-Cdh1(Fzr) and is required to prevent cyclin degradation in G2. Developmental Cell 2, 2940.

R. S. Hames , S. L. Wattam , H. Yamano , R. Bacchieri & A. M. Fry (2001). APC/C-mediated destruction of the centrosomal kinase Nek2A occurs in early mitosis and depends upon a cyclin A-type D-box. Embo Journal 20, 71177127.

D. Han , K. Kim , Y. Kim , Y. Kang , J. Y. Lee & Y. Kim (2009). Crystal structure of the N-terminal domain of anaphase-promoting complex subunit 7. Journal of Biological Chemistry 284, 1513715146.

D. V. Hansen , A. V. Loktev , K. H. Ban & P. K. Jackson (2004). Plk1 regulates activation of the anaphase promoting complex by phosphorylating and triggering SCFbetaTrCP-dependent destruction of the APC Inhibitor Emi1. Molecular Biology of the Cell 15, 56235634.

K. G. Hardwick , R. C. Johnston , D. L. Smith & A. W. Murray (2000). MAD3 encodes a novel component of the spindle checkpoint which interacts with Bub3p, Cdc20p, and Mad2p. Journal of Cell Biology 148, 871882.

J. W. Harper , J. L. Burton & M. J. Solomon (2002). The anaphase-promoting complex: it's not just for mitosis any more. Genes and Development 16, 21792206.

M. J. Hayes , Y. Kimata , S. L. Wattam , C. Lindon , G. Mao , H. Yamano & A. M. Fry (2006). Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with the APC/C. Nature Cell Biology 8, 607614.

C. Hendrickson , M. A. Meyn III, L. Morabito & S. L. Holloway (2001). The KEN box regulates Clb2 proteolysis in G1 and at the metaphase-to-anaphase transition. Current Biology 11, 17811787.

A. Herrero-Mendez , A. Almeida , E. Fernandez , C. Maestre , S. Moncada & J. P. Bolanos (2009). The bioenergetic and antioxidant status of neurons is controlled by continuous degradation of a key glycolytic enzyme by APC/C-Cdh1. Nature Cell Biology 11, 747752.

A. Hershko & A. Ciechanover (1998). The ubiquitin system. Annual Review of Biochemistry 67, 425479.

F. Herzog , I. Primorac , P. Dube , P. Lenart , B. Sander , K. Mechtler , H. Stark & J. M. Peters (2009). Structure of the anaphase-promoting complex/cyclosome interacting with a mitotic checkpoint complex. Science 323, 14771481.

E. R. Hildebrandt & M. A. Hoyt (2001). Cell cycle-dependent degradation of the Saccharomyces cerevisiae spindle motor Cin8p requires APC(Cdh1) and a bipartite destruction sequence. Molecular Biology of the Cell 12, 34023416.

Z. Hilioti , Y. S. Chung , Y. Mochizuki , C. F. Hardy & O. Cohen-Fix (2001). The anaphase inhibitor Pds1 binds to the APC/C-associated protein Cdc20 in a destruction box-dependent manner. Current Biology 11, 13471352.

T. Hirano , N. Kinoshita , K. Morikawa & M. Yanagida (1990). Snap helix with knob and hole: essential repeats in S. pombe nuclear protein nuc2+. Cell 60, 319328.

M. Hochstrasser (2006). Lingering mysteries of ubiquitin-chain assembly. Cell 124, 2734.

A. J. Holland & S. S. Taylor (2006). Cyclin-B1-mediated inhibition of excess separase is required for timely chromosome disjunction. Journal of Cell Science 119, 33253336.

L. J. Holt , A. N. Krutchinsky & D. O. Morgan (2008). Positive feedback sharpens the anaphase switch. Nature 454, 353357.

J. Y. Hsu , J. D. Reimann , C. S. Sorensen , J. Lukas & P. K. Jackson (2002). E2F-dependent accumulation of hEmi1 regulates S phase entry by inhibiting APC(Cdh1). Nature Cell Biology 4, 358366.

J. R. Hutchins , Y. Toyoda , B. Hegemann , I. Poser , J. K. Heriche , M. M. Sykora , M. Augsburg , O. Hudecz , B. A. Buschhorn , J. Bulkescher , C. Conrad , D. Comartin , A. Schleiffer , M. Sarov , A. Pozniakovsky , M. M. Slabicki , S. Schloissnig , I. Steinmacher , M. Leuschner , A. Ssykor , S. Lawo , L. Pelletier , H. Stark , K. Nasmyth , J. Ellenberg , R. Durbin , F. Buchholz , K. Mechtler , A. A. Hyman & J. M. Peters (2010). Systematic analysis of human protein complexes identifies chromosome segregation proteins. Science 328, 593599.

L. H. Hwang , L. F. Lau , D. L. Smith , C. A. Mistrot , K. G. Hardwick , E. S. Hwang , A. Amon & A. W. Murray (1998). Budding yeast Cdc20: a target of the spindle checkpoint. Science 279, 10411044.

L. H. Hwang & A. W. Murray (1997). A novel yeast screen for mitotic arrest mutants identifies DOC1, a new gene involved in cyclin proteolysis. Molecular Biology of the Cell 8, 18771887.

D. Inoue , M. Ohe , Y. Kanemori , T. Nobui & N. Sagata (2007). A direct link of the Mos-MAPK pathway to Erp1/Emi2 in meiotic arrest of Xenopus laevis eggs. Nature 446, 11001104.

S. Irniger , S. Piatti , C. Michaelis & K. Nasmyth (1995). Genes involved in sister chromatid separation are needed for B-type cyclin proteolysis in budding yeast. Cell 81, 269278.

H. W. Jacobs , E. Keidel & C. F. Lehner (2001). A complex degradation signal in Cyclin A required for G1 arrest, and a C-terminal region for mitosis. Embo Journal 20, 23762386.

S. L. Jaspersen , J. F. Charles & D. O. Morgan (1999). Inhibitory phosphorylation of the APC regulator Hct1 is controlled by the kinase Cdc28 and the phosphatase Cdc14. Current Biology 9, 227236.

L. Jin , A. Williamson , S. Banerjee , I. Philipp & M. Rape (2008). Mechanism of ubiquitin-chain formation by the human anaphase-promoting complex. Cell 133, 653665.

A. V. Kajava (2002). What curves alpha-solenoids? Evidence for an alpha-helical toroid structure of Rpn1 and Rpn2 proteins of the 26 S proteasome. Journal of Biological Chemistry 277, 4979149798.

T. Kaneko , J. Hamazaki , S. Iemura , K. Sasaki , K. Furuyama , T. Natsume , K. Tanaka & S. Murata (2009). Assembly pathway of the Mammalian proteasome base subcomplex is mediated by multiple specific chaperones. Cell 137, 914925.

A. H. Kim , S. V. Puram , P. M. Bilimoria , Y. Ikeuchi , S. Keough , M. Wong , D. Rowitch & A. Bonni (2009). A centrosomal Cdc20-APC pathway controls dendrite morphogenesis in postmitotic neurons. Cell 136, 322336.

S. H. Kim , D. P. Lin , S. Matsumoto , A. Kitazono & T. Matsumoto (1998). Fission yeast Slp1: an effector of the Mad2-dependent spindle checkpoint. Science 279, 10451047.

Y. Kimata , J. E. Baxter , A. M. Fry & H. Yamano (2008a). A role for the Fizzy/Cdc20 family of proteins in activation of the APC/C distinct from substrate recruitment. Molecular Cell 32, 576583.

Y. Kimata , M. Trickey , D. Izawa , J. Gannon , M. Yamamoto & H. Yamano (2008b). A mutual inhibition between APC/C and its substrate Mes1 required for meiotic progression in fission yeast. Developmental Cell 14, 446454.

E. M. King , S. J. van Der Sar & K. G. Hardwick (2007). Mad3 KEN boxes mediate both Cdc20 and Mad3 turnover, and are critical for the spindle checkpoint. PLoS ONE 2, e342.

R. W. King , M. Glotzer & M. W. Kirschner (1996). Mutagenic analysis of the destruction signal of mitotic cyclins and structural characterization of ubiquitinated intermediates. Molecular Biology of the Cell 7, 13431357.

R. W. King , J. M. Peters , S. Tugendreich , M. Rolfe , P. Hieter & M. W. Kirschner (1995). A 20S complex containing CDC27 and CDC16 catalyzes the mitosis-specific conjugation of ubiquitin to cyclin B. Cell 81, 279288.

D. S. Kirkpatrick , N. A. Hathaway , J. Hanna , S. Elsasser , J. Rush , D. Finley , R. W. King & S. P. Gygi (2006). Quantitative analysis of in vitro ubiquitinated cyclin B1 reveals complex chain topology. Nature Cell Biology 8, 700710.

G. Kleiger , A. Saha , S. Lewis , B. Kuhlman & R. J. Deshaies (2009). Rapid E2-E3 assembly and disassembly enable processive ubiquitylation of cullin-RING ubiquitin ligase substrates. Cell 139, 957968.

D. Komander , F. Reyes-Turcu , J. D. Licchesi , P. Odenwaelder , K. D. Wilkinson & D. Barford (2009). Molecular discrimination of structurally equivalent Lys 63-linked and linear polyubiquitin chains. EMBO Reports 10, 466473.

K. Kominami , H. Seth-Smith & T. Toda (1998). 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. EMBO Journal 17, 53885399.

G. J. Kops , M. V. Voet , M. S. Manak , M. H. Van Osch , S. M. Naini , A. Brear , I. X. Mcleod , D. M. Hentschel , J. R. Yates III, S. van Den Heuvel & J. V. Shah (2010). APC16 is a conserved subunit of the anaphase-promoting complex/cyclosome. Journal of Cell Science 123, 16231633.

C. Kraft , F. Herzog , C. Gieffers , K. Mechtler , A. Hagting , J. Pines & J. M. Peters (2003). Mitotic regulation of the human anaphase-promoting complex by phosphorylation. Embo Journal 22, 65986609.

C. Kraft , H. C. Vodermaier , S. Maurer-Stroh , F. Eisenhaber & J. M. Peters (2005). The WD40 propeller domain of Cdh1 functions as a destruction box receptor for APC/C substrates. Molecular Cell 18, 543553.

E. R. Kramer , C. Gieffers , G. Holzl , M. Hengstschlager & J. M. Peters (1998a). Activation of the human anaphase-promoting complex by proteins of the CDC20/Fizzy family. Current Biology 8, 12071210.

E. R. Kramer , N. Scheuringer , A. V. Podtelejnikov , M. Mann & J. M. Peters (2000). Mitotic regulation of the APC activator proteins CDC20 and CDH1. Molecular Biology of the Cell 11, 15551569.

K. M. Kramer , D. Fesquet , A. L. Johnson & L. H. Johnston (1998b). Budding yeast RSI1/APC2, a novel gene necessary for initiation of anaphase, encodes an APC subunit. Embo Journal 17, 498506.

Y. Kravtsova-Ivantsiv , S. Cohen & A. Ciechanover (2009). Modification by single ubiquitin moieties rather than polyubiquitination is sufficient for proteasomal processing of the p105 NF-kappaB precursor. Molecular Cell 33, 496504.

A. Kulukian , J. S. Han & D. W. Cleveland (2009). Unattached kinetochores catalyze production of an anaphase inhibitor that requires a Mad2 template to prime Cdc20 for BubR1 binding. Developmental Cell 16, 105117.

Y. Kurasawa & K. Todokoro (1999). Identification of human APC10/Doc1 as a subunit of anaphase promoting complex. Oncogene 18, 51315137.

S. Lahav-Baratz , V. Sudakin , J. V. Ruderman & A. Hershko (1995). Reversible phosphorylation controls the activity of cyclosome-associated cyclin-ubiquitin ligase. Proceedings of the National Academy of Sciences of the United States of America 92, 93039307.

N. A. Larsen , J. Al-Bassam , R. R. Wei & S. C. Harrison (2007). Structural analysis of Bub3 interactions in the mitotic spindle checkpoint. Proceedings of the National Academy of Sciences of the United States of America 104, 12011206.

J. D. Leverson , C. A. Joazeiro , A. M. Page , H. Huang , P. Hieter & T. Hunter (2000). The APC11 RING-H2 finger mediates E2-dependent ubiquitination. Molecular Biology of the Cell 11, 23152325.

M. Li , Y. H. Shin , L. Hou , X. Huang , Z. Wei , E. Klann & P. Zhang (2008). The adaptor protein of the anaphase promoting complex Cdh1 is essential in maintaining replicative lifespan and in learning and memory. Nature Cell Biology 10, 10831089.

W. Li , D. Tu , A. T. Brunger & Y. Ye (2007). A ubiquitin ligase transfers preformed polyubiquitin chains from a conjugating enzyme to a substrate. Nature 446, 333337.

H. H. Lim , P. Y. Goh & U. Surana (1998). Cdc20 is essential for the cyclosome-mediated proteolysis of both Pds1 and Clb2 during M phase in budding yeast. Current Biology 8, 231234.

L. E. Littlepage & J. V. Ruderman (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 and Development 16, 22742285.

J. Liu & J. L. Maller (2005). Calcium elevation at fertilization coordinates phosphorylation of XErp1/Emi2 by Plx1 and CaMK II to release metaphase arrest by cytostatic factor. Current Biology 15, 14581468.

T. Lorca , A. Castro , A. M. Martinez , S. Vigneron , N. Morin , S. Sigrist , C. Lehner , M. Doree & J. C. Labbe (1998). Fizzy is required for activation of the APC/cyclosome in Xenopus egg extracts. Embo Journal 17, 35653575.

X. Luo , Z. Tang , J. Rizo & H. Yu (2002). The Mad2 spindle checkpoint protein undergoes similar major conformational changes upon binding to either Mad1 or Cdc20. Molecular Cell 9, 5971.

X. Luo & H. Yu (2008). Protein metamorphosis: the two-state behavior of Mad2. Structure 16, 16161625.

A. Lupas , W. Baumeister & K. Hofmann (1997). A repetitive sequence in subunits of the 26S proteasome and 20S cyclosome (anaphase-promoting complex). Trends in Biochemical Sciences 22, 195196.

N. Mailand & J. F. Diffley (2005). CDKs promote DNA replication origin licensing in human cells by protecting Cdc6 from APC/C-dependent proteolysis. Cell 122, 915926.

L. A. Malureanu , K. B. Jeganathan , M. Hamada , L. Wasilewski , J. Davenport & J. M. Van Deursen (2009). BubR1 N terminus acts as a soluble inhibitor of cyclin B degradation by APC/C(Cdc20) in interphase. Developmental Cell 16, 118131.

M. Mapelli , L. Massimiliano , S. Santaguida & A. Musacchio (2007). The Mad2 conformational dimer: structure and implications for the spindle assembly checkpoint. Cell 131, 730743.

P. Marangos & J. Carroll (2008). Securin regulates entry into M-phase by modulating the stability of cyclin B. Nature Cell Biology 10, 445451.

J. S. Martinez , D. E. Jeong , E. Choi , B. M. Billings & M. C. Hall (2006). Acm1 is a negative regulator of the CDH1-dependent anaphase-promoting complex/cyclosome in budding yeast. Molecular and Cellular Biology 26, 91629176.

Y. Masui & C. L. Markert (1971). Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. Journal of Experimental Zoology 177, 129145.

E. Mathe , C. Kraft , R. Giet , P. Deak , J. M. Peters & D. M. Glover (2004). The E2-C vihar is required for the correct spatiotemporal proteolysis of cyclin B and itself undergoes cyclical degradation. Current Biology 14, 17231733.

M. E. Matyskiela & D. O. Morgan (2009). Analysis of activator-binding sites on the APC/C supports a cooperative substrate-binding mechanism. Molecular Cell 34, 6880.

Y. Merbl & M. W. Kirschner (2009). Large-scale detection of ubiquitination substrates using cell extracts and protein microarrays. Proceedings of the National Academy of Sciences of the United States of America 106, 25432548.

C. Michaelis , R. Ciosk & K. Nasmyth (1997). Cohesins: chromosomal proteins that prevent premature separation of sister chromatids. Cell 91, 3545.

J. J. Miller , M. K. Summers , D. V. Hansen , M. V. Nachury , N. L. Lehman , A. Loktev & P. K. Jackson (2006). Emi1 stably binds and inhibits the anaphase-promoting complex/cyclosome as a pseudosubstrate inhibitor. Genes and Development 20, 24102420.

S. Mochida & T. Hunt (2007). Calcineurin is required to release Xenopus egg extracts from meiotic M phase. Nature 449, 336340.

S. Murata , H. Yashiroda & K. Tanaka (2009). Molecular mechanisms of proteasome assembly. Nature Reviews Molecular Cell Biology 10, 104115.

A. W. Murray , M. J. Solomon & M. W. Kirschner (1989). The role of cyclin synthesis and degradation in the control of maturation promoting factor activity. Nature 339, 280286.

A. Musacchio & E. D. Salmon (2007). The spindle-assembly checkpoint in space and time. Nature Reviews Molecular Cell Biology 8, 379393.

K. Nasmyth (2002). Segregating sister genomes: the molecular biology of chromosome separation. Science 297, 559565.

J. Nilsson , M. Yekezare , J. Minshull & J. Pines (2008). The APC/C maintains the spindle assembly checkpoint by targeting Cdc20 for destruction. Nature Cell Biology 10, 14111420.

T. Nishiyama , K. Ohsumi & T. Kishimoto (2007a). Phosphorylation of Erp1 by p90rsk is required for cytostatic factor arrest in Xenopus laevis eggs. Nature 446, 10961099.

T. Nishiyama , N. Yoshizaki , T. Kishimoto & K. Ohsumi (2007b). Transient activation of calcineurin is essential to initiate embryonic development in Xenopus laevis. Nature 449, 341345.

E. Noton & J. F. Diffley (2000). CDK inactivation is the only essential function of the APC/C and the mitotic exit network proteins for origin resetting during mitosis. Molecular Cell 5, 8595.

T. Oelschlaegel , M. Schwickart , J. Matos , A. Bogdanova , A. Camasses , J. Havlis , A. Shevchenko & W. Zachariae (2005). The yeast APC/C subunit Mnd2 prevents premature sister chromatid separation triggered by the meiosis-specific APC/C-Ama1. Cell 120, 773788.

M. D. Ohi , A. Feoktistova , L. Ren , C. Yip , Y. Cheng , J. S. Chen , H. J. Yoon , J. S. Wall , Z. Huang , P. A. Penczek , K. L. Gould & T. Walz (2007). Structural organization of the anaphase-promoting complex bound to the mitotic activator Slp1. Molecular Cell 28, 871885.

F. Osaka , H. Seino , T. Seno & F. Yamao (1997). A ubiquitin-conjugating enzyme in fission yeast that is essential for the onset of anaphase in mitosis. Molecular and Cellular Biology 17, 33883397.

D. Ostapenko , J. L. Burton , R. Wang & M. J. Solomon (2008). Pseudosubstrate inhibition of the anaphase-promoting complex by Acm1: regulation by proteolysis and Cdc28 phosphorylation. Molecular and Cellular Biology 28, 46534664.

J. Pan & R. H. Chen (2004). Spindle checkpoint regulates Cdc20p stability in Saccharomyces cerevisiae. Genes and Development 18, 14391451.

L. A. Passmore & D. Barford (2004). Getting into position: the catalytic mechanisms of protein ubiquitylation. Biochemical Journal 379, 513525.

L. A. Passmore & D. Barford (2005). Coactivator functions in a stoichiometric complex with anaphase-promoting complex/cyclosome to mediate substrate recognition. EMBO Reports 6, 873878.

L. A. Passmore , C. R. Booth , C. Venien-Bryan , S. J. Ludtke , C. Fioretto , L. N. Johnson , W. Chiu & D. Barford (2005). Structural analysis of the anaphase-promoting complex reveals multiple active sites and insights into polyubiquitylation. Molecular Cell 20, 855866.

L. A. Passmore , E. A. Mccormack , S. W. Au , A. Paul , K. R. Willison , J. W. Harper & D. Barford (2003). Doc1 mediates the activity of the anaphase-promoting complex by contributing to substrate recognition. Embo Journal 22, 786796.

A. M. Penkner , S. Prinz , S. Ferscha & F. Klein (2005). Mnd2, an essential antagonist of the anaphase-promoting complex during meiotic prophase. Cell 120, 789801.

J. M. Peters (2006). The anaphase promoting complex/cyclosome: a machine designed to destroy. Nature Reviews Molecular Cell Biology 7, 644656.

J. M. Peters , R. W. King , C. Hoog & M. W. Kirschner (1996). Identification of BIME as a subunit of the anaphase-promoting complex. Science 274, 11991201.

M. D. Petroski & R. J. Deshaies (2005). Function and regulation of cullin-RING ubiquitin ligases. Nature Reviews Molecular Cell Biology 6, 920.

C. M. Pfleger , E. Lee & M. W. Kirschner (2001). Substrate recognition by the Cdc20 and Cdh1 components of the anaphase-promoting complex. Genes and Development 15, 23962407.

C. M. Pickart (2001). Mechanisms underlying ubiquitination. Annual Review of Biochemistry 70, 503533.

N. W. Pierce , G. Kleiger , S. O. Shan & R. J. Deshaies (2009). Detection of sequential polyubiquitylation on a millisecond timescale. Nature 462, 615619.

J. Pines (2006). Mitosis: a matter of getting rid of the right protein at the right time. Trends in Cell Biology 16, 5563.

S. Rankin , N. G. Ayad & M. W. Kirschner (2005). Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates. Molecular Cell 18, 185200.

M. Rape & M. W. Kirschner (2004). Autonomous regulation of the anaphase-promoting complex couples mitosis to S-phase entry. Nature 432, 588595.

M. Rape , S. K. Reddy & M. W. Kirschner (2006). The processivity of multiubiquitination by the APC determines the order of substrate degradation. Cell 124, 89103.

N. R. Rauh , A. Schmidt , J. Bormann , E. A. Nigg & T. U. Mayer (2005). Calcium triggers exit from meiosis II by targeting the APC/C inhibitor XErp1 for degradation. Nature 437, 10481052.

T. Ravid & M. Hochstrasser (2007). Autoregulation of an E2 enzyme by ubiquitin-chain assembly on its catalytic residue. Nature Cell Biology 9, 422427.

S. K. Reddy , M. Rape , W. A. Margansky & M. W. Kirschner (2007). Ubiquitination by the anaphase-promoting complex drives spindle checkpoint inactivation. Nature 446, 921925.

J. D. Reimann , E. Freed , J. Y. Hsu , E. R. Kramer , J. M. Peters & P. K. Jackson (2001a). Emi1 is a mitotic regulator that interacts with Cdc20 and inhibits the anaphase promoting complex. Cell 105, 645655.

J. D. Reimann , B. E. Gardner , F. Margottin-Goguet & P. K. Jackson (2001b). Emi1 regulates the anaphase-promoting complex by a different mechanism than Mad2 proteins. Genes and Development 15, 32783285.

A. Reis , M. Levasseur , H. Y. Chang , D. J. Elliott & K. T. Jones (2006). The CRY box: a second APCcdh1-dependent degron in mammalian cdc20. EMBO Reports 7, 10401045.

D. Reverter & C. D. Lima (2005). Insights into E3 ligase activity revealed by a SUMO-RanGAP1-Ubc9-Nup358 complex. Nature 435, 687692.

C. L. Rieder , R. W. Cole , A. Khodjakov & G. Sluder (1995). The checkpoint delaying anaphase in response to chromosome monoorientation is mediated by an inhibitory signal produced by unattached kinetochores. Journal of Cell Biology 130, 941948.

C. L. Rieder , A. Schultz , R. Cole & G. Sluder (1994). Anaphase onset in vertebrate somatic cells is controlled by a checkpoint that monitors sister kinetochore attachment to the spindle. Journal of Cell Biology 127, 13011310.

M. C. Rodrigo-Brenni & D. O. Morgan (2007). Sequential E2s drive polyubiquitin chain assembly on APC targets. Cell 130, 127139.

J. Roelofs , S. Park , W. Haas , G. Tian , F. E. Mcallister , Y. Huo , B. H. Lee , F. Zhang , Y. Shi , S. P. Gygi & D. Finley (2009). Chaperone-mediated pathway of proteasome regulatory particle assembly. Nature 459, 861865.

D. Rotin & S. Kumar (2009). Physiological functions of the HECT family of ubiquitin ligases. Nature Reviews Molecular Cell Biology 10, 398409.

A. D. Rudner & A. W. Murray (2000). Phosphorylation by Cdc28 activates the Cdc20-dependent activity of the anaphase-promoting complex. Journal of Cell Biology 149, 13771390.

Y. Saeki , T. Kudo , T. Sone , Y. Kikuchi , H. Yokosawa , A. Toh-E & K. Tanaka (2009a). Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome. Embo Journal 28, 359371.

Y. Saeki , E. A. Toh , T. Kudo , H. Kawamura & K. Tanaka (2009b). Multiple proteasome-interacting proteins assist the assembly of the yeast 19S regulatory particle. Cell 137, 900913.

N. Sagata , N. Watanabe , G. F. Vande Woude & Y. Ikawa (1989). The c-mos proto-oncogene product is a cytostatic factor responsible for meiotic arrest in vertebrate eggs. Nature 342, 512518.

A. Saha & R. J. Deshaies (2008). Multimodal activation of the ubiquitin ligase SCF by Nedd8 conjugation. Molecular Cell 32, 2131.

M. Schwab , A. S. Lutum & W. Seufert (1997). Yeast Hct1 is a regulator of Clb2 cyclin proteolysis. Cell 90, 683693.

M. Schwab , M. Neutzner , D. Mocker & W. Seufert (2001). Yeast Hct1 recognizes the mitotic cyclin Clb2 and other substrates of the ubiquitin ligase APC. Embo Journal 20, 51655175.

M. Schwickart , J. Havlis , B. Habermann , A. Bogdanova , A. Camasses , T. Oelschlaegel , A. Shevchenko & W. Zachariae (2004). Swm1/Apc13 is an evolutionarily conserved subunit of the anaphase-promoting complex stabilizing the association of Cdc16 and Cdc27. Molecular and Cellular Biology 24, 35623576.

M. Sczaniecka , A. Feoktistova , K. M. May , J. S. Chen , J. Blyth , K. L. Gould & K. G. Hardwick (2008). The spindle checkpoint functions of Mad3 and Mad2 depend on a Mad3 KEN box-mediated interaction with Cdc20-anaphase-promoting complex (APC/C). Journal of Biological Chemistry 283, 2303923047.

M. Shirayama , W. Zachariae , R. Ciosk & K. Nasmyth (1998). The Polo-like kinase Cdc5p and the WD-repeat protein Cdc20p/fizzy are regulators and substrates of the anaphase promoting complex in Saccharomyces cerevisiae. Embo Journal 17, 13361349.

W. Shou , J. H. Seol , A. Shevchenko , C. Baskerville , D. Moazed , Z. W. Chen , J. Jang , A. Shevchenko , H. Charbonneau & R. J. Deshaies (1999). Exit from mitosis is triggered by Tem1-dependent release of the protein phosphatase Cdc14 from nucleolar RENT complex. Cell 97, 233244.

M. Shteinberg , Y. Protopopov , T. Listovsky , M. Brandeis & A. Hershko (1999). Phosphorylation of the cyclosome is required for its stimulation by Fizzy/cdc20. Biochemical and Biophysical Research Communication 260, 193198.

S. J. Sigrist & C. F. Lehner (1997). Drosophila fizzy-related down-regulates mitotic cyclins and is required for cell proliferation arrest and entry into endocycles. Cell 90, 671681.

R. S. Sikorski , M. S. Boguski , M. Goebl & P. Hieter (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, 307317.

R. S. Sikorski , W. A. Michaud & P. Hieter (1993). p62cdc23 of Saccharomyces cerevisiae: a nuclear tetratricopeptide repeat protein with two mutable domains. Molecular and Cellular Biology 13, 12121221.

R. S. Sikorski , W. A. Michaud , J. C. Wootton , M. S. Boguski , C. Connelly & P. Hieter (1991). TPR proteins as essential components of the yeast cell cycle. Cold Spring Harbor Symposia on Quantitative Biology 56, 663673.

L. Sironi , M. Mapelli , S. Knapp , A. De Antoni , K. T. Jeang & A. Musacchio (2002). Crystal structure of the tetrameric Mad1–Mad2 core complex: implications of a ‘safety belt’ binding mechanism for the spindle checkpoint. Embo Journal 21, 24962506.

M. J. Solomon & J. L. Burton (2008). Securin' M-phase entry. Nature Cell Biology 10, 381383.

J. A. Steen , H. Steen , A. Georgi , K. Parker , M. Springer , M. Kirchner , F. Hamprecht & M. W. Kirschner (2008). Different phosphorylation states of the anaphase promoting complex in response to antimitotic drugs: a quantitative proteomic analysis. Proceedings of the National Academy of Sciences of the United States of America 105, 60696074.

F. Stegmeier , M. Rape , V. M. Draviam , G. Nalepa , M. E. Sowa , X. L. Ang , E. R. Mcdonald III, M. Z. Li , G. J. Hannon , P. K. Sorger , M. W. Kirschner , J. W. Harper & S. J. Elledge (2007). Anaphase initiation is regulated by antagonistic ubiquitination and deubiquitination activities. Nature 446, 876881.

O. Stemmann , H. Zou , S. A. Gerber , S. P. Gygi & M. W. Kirschner (2001). Dual inhibition of sister chromatid separation at metaphase. Cell 107, 715726.

V. Sudakin , G. K. Chan & T. J. Yen (2001). Checkpoint inhibition of the APC/C in HeLa cells is mediated by a complex of BUBR1, BUB3, CDC20, and MAD2. Journal of Cell Biology 154, 925936.

V. Sudakin , D. Ganoth , A. Dahan , H. Heller , J. Hershko , F. C. Luca , J. V. Ruderman & A. Hershko (1995). The cyclosome, a large complex containing cyclin-selective ubiquitin ligase activity, targets cyclins for destruction at the end of mitosis. Molecular Biology of the Cell 6, 185197.

M. Sullivan & D. O. Morgan (2007a). A novel destruction sequence targets the meiotic regulator Spo13 for anaphase-promoting complex-dependent degradation in anaphase I. Journal of Biological Chemistry 282, 1971019715.

M. Sullivan & D. O. Morgan (2007b). Finishing mitosis, one step at a time. Nat Rev Molecular and Cellular Biology 8, 894903.

M. K. Summers , B. Pan , K. Mukhyala & P. K. Jackson (2008). The unique N terminus of the UbcH10 E2 enzyme controls the threshold for APC activation and enhances checkpoint regulation of the APC. Molecular Cell 31, 544556.

Z. Tang , R. Bharadwaj , B. Li & H. Yu (2001a). Mad2-Independent inhibition of APCCdc20 by the mitotic checkpoint protein BubR1. Developmental Cell 1, 227237.

Z. Tang , B. Li , R. Bharadwaj , H. Zhu , E. Ozkan , K. Hakala , J. Deisenhofer & H. Yu (2001b). APC2 Cullin protein and APC11 RING protein comprise the minimal ubiquitin ligase module of the anaphase-promoting complex. Molecular Biology of the Cell 12, 38393851.

Z. Tang , H. Shu , D. Oncel , S. Chen & H. Yu (2004). Phosphorylation of Cdc20 by Bub1 provides a catalytic mechanism for APC/C inhibition by the spindle checkpoint. Molecular Cell 16, 387397.

B. R. Thornton , T. M. Ng , M. E. Matyskiela , C. W. Carroll , D. O. Morgan & D. P. Toczyski (2006). An architectural map of the anaphase-promoting complex. Genes and Development 20, 449460.

B. R. Thornton & D. P. Toczyski (2003). Securin and B-cyclin/CDK are the only essential targets of the APC. Nature Cell Biology 5, 10901094.

B. R. Thornton & D. P. Toczyski (2006). Precise destruction: an emerging picture of the APC. Genes and Development 20, 30693078.

J. S. Thrower , L. Hoffman , M. Rechsteiner & C. M. Pickart (2000). Recognition of the polyubiquitin proteolytic signal. Embo Journal 19, 94102.

S. Tugendreich , J. Tomkiel , W. Earnshaw & P. Hieter (1995). CDC27Hs colocalizes with CDC16Hs to the centrosome and mitotic spindle and is essential for the metaphase to anaphase transition. Cell 81, 261268.

J. J. Tung , D. V. Hansen , K. H. Ban , A. V. Loktev , M. K. Summers , J. R. Adler III & P. K. Jackson (2005). A role for the anaphase-promoting complex inhibitor Emi2/XErp1, a homolog of early mitotic inhibitor 1, in cytostatic factor arrest of Xenopus eggs. Proceedings of the National Academy of Sciences of the United States of America 102, 43184323.

F. Uhlmann , D. Wernic , M. A. Poupart , E. V. Koonin & K. Nasmyth (2000). Cleavage of cohesin by the CD clan protease separin triggers anaphase in yeast. Cell 103, 375386.

P. Van Roessel , D. A. Elliott , I. M. Robinson , A. Prokop & A. H. Brand (2004). Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell 119, 707718.

R. Visintin , K. Craig , E. S. Hwang , S. Prinz , M. Tyers & A. Amon (1998). The phosphatase Cdc14 triggers mitotic exit by reversal of Cdk-dependent phosphorylation. Molecular Cell 2, 709718.

R. Visintin , S. Prinz & A. Amon (1997). CDC20 and CDH1: a family of substrate-specific activators of APC-dependent proteolysis. Science 278, 460463.

H. C. Vodermaier , C. Gieffers , S. Maurer-Stroh , F. Eisenhaber & J. M. Peters (2003). TPR subunits of the anaphase-promoting complex mediate binding to the activator protein CDH1. Current Biology 13, 14591468.

H. C. Vodermaier & J. M. Peters (2004). APC activators caught by their tails? Cell Cycle 3, 265266.

A. Walker , C. Acquaviva , T. Matsusaka , L. Koop & J. Pines (2008). UbcH10 has a rate-limiting role in G1 phase but might not act in the spindle checkpoint or as part of an autonomous oscillator. Journal of Cell Science 121, 23192326.

J. Wang , B. T. Dye , K. R. Rajashankar , I. Kurinov & B. A. Schulman (2009). Insights into anaphase promoting complex TPR subdomain assembly from a CDC26-APC6 structure. Nature Structural and Molecular Biology 16, 987989.

R. Wasch & F. R. Cross (2002). APC-dependent proteolysis of the mitotic cyclin Clb2 is essential for mitotic exit. Nature 418, 556562.

K. S. Wendt , H. C. Vodermaier , U. Jacob , C. Gieffers , M. Gmachl , J. M. Peters , R. Huber & P. Sondermann (2001). Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex. Nature Structural Biology 8, 784788.

A. Williamson , K. E. Wickliffe , B. G. Mellone , L. Song , G. H. Karpen & M. Rape (2009). Identification of a physiological E2 module for the human anaphase-promoting complex. Proceedings of the National Academy of Sciences of the United States of America 106, 1821318218.

R. Wolthuis , L. Clay-Farrace , W. Van Zon , M. Yekezare , L. Koop , J. Ogink , R. Medema & J. Pines (2008). Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A. Molecular Cell 30, 290302.

P. Y. Wu , M. Hanlon , M. Eddins , C. Tsui , R. S. Rogers , J. P. Jensen , M. J. Matunis , A. M. Weissman , C. Wolberger & C. M. Pickart (2003). A conserved catalytic residue in the ubiquitin-conjugating enzyme family. Embo Journal 22, 52415250.

T. Wu , Y. Merbl , Y. Huo , J. L. Gallop , A. Tzur & M. W. Kirschner (2010). UBE2S drives elongation of K11-linked ubiquitin chains by the anaphase-promoting complex. Proceedings of the National Academy of Sciences of the United States of America 107, 13551360.

P. Xu , D. M. Duong , N. T. Seyfried , D. Cheng , Y. Xie , J. Robert , J. Rush , M. Hochstrasser , D. Finley & J. Peng (2009). Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell 137, 133145.

H. Yamano , J. Gannon , H. Mahbubani & T. Hunt (2004). Cell cycle-regulated recognition of the destruction box of cyclin B by the APC/C in Xenopus egg extracts. Molecular Cell 13, 137147.

H. Yamano , C. Tsurumi , J. Gannon & T. Hunt (1998). The role of the destruction box and its neighbouring lysine residues in cyclin B for anaphase ubiquitin-dependent proteolysis in fission yeast: defining the D-box receptor. Embo Journal 17, 56705678.

M. Yang , B. Li , C. J. Liu , D. R. Tomchick , M. Machius , J. Rizo , H. Yu & X. Luo (2008). Insights into mad2 regulation in the spindle checkpoint revealed by the crystal structure of the symmetric mad2 dimer. PLoS Biology 6, e50.

Y. Ye & M. Rape (2009). Building ubiquitin chains: E2 enzymes at work. Nature Reviews Molecular Cell Biology 10, 755764.

H. J. Yoon , A. Feoktistova , J. S. Chen , J. L. Jennings , A. J. Link & K. L. Gould (2006). Role of Hcn1 and its phosphorylation in fission yeast anaphase-promoting complex/cyclosome function. Journal of Biological Chemistry 281, 3228432293.

H. J. Yoon , A. Feoktistova , B. A. Wolfe , J. L. Jennings , A. J. Link & K. L. Gould (2002). Proteomics analysis identifies new components of the fission and budding yeast anaphase-promoting complexes. Current Biology 12, 20482054.

H. Yu (2007). Cdc20: a WD40 activator for a cell cycle degradation machine. Molecular Cell 27, 316.

H. Yu , R. W. King , J. M. Peters & M. W. Kirschner (1996). Identification of a novel ubiquitin-conjugating enzyme involved in mitotic cyclin degradation. Current Biology 6, 455466.

H. Yu , J. M. Peters , R. W. King , A. M. Page , P. Hieter & M. W. Kirschner (1998). Identification of a cullin homology region in a subunit of the anaphase-promoting complex. Science 279, 12191222.

Y. Yudkovsky , M. Shteinberg , T. Listovsky , M. Brandeis & A. Hershko (2000). Phosphorylation of Cdc20/fizzy negatively regulates the mammalian cyclosome/APC in the mitotic checkpoint. Biochemical and Biophysical Research Communication 271, 299304.

A. A. Yunus & C. D. Lima (2006). Lysine activation and functional analysis of E2-mediated conjugation in the SUMO pathway. Nature Structural and Molecular Biology 13, 491499.

W. Zachariae & K. Nasmyth (1996). TPR proteins required for anaphase progression mediate ubiquitination of mitotic B-type cyclins in yeast. Molecular Biology of the Cell 7, 791801.

W. Zachariae , M. Schwab , K. Nasmyth & W. Seufert (1998a). Control of cyclin ubiquitination by CDK-regulated binding of Hct1 to the anaphase promoting complex. Science 282, 17211724.

W. Zachariae , A. Shevchenko , P. D. Andrews , R. Ciosk , M. Galova , M. J. Stark , M. Mann & K. Nasmyth (1998b). Mass spectrometric analysis of the anaphase-promoting complex from yeast: identification of a subunit related to cullins. Science 279, 12161219.

W. Zachariae , T. H. Shin , M. Galova , B. Obermaier & K. Nasmyth (1996). Identification of subunits of the anaphase-promoting complex of Saccharomyces cerevisiae. Science 274, 12011204.

Z. Zhang , S. M. Roe , M. Diogon , E. Kong , H. El Alaoui & D. Barford (2010a). Molecular structure of the N-terminal domain of the APC/C subunit Cdc27 reveals a homo-dimeric tetratricopeptide repeat architecture. Journal of Molecular Biology 397, 13161328.

Z. Zhang , K. Kulkarni , S. J. Hanrahan , A. J. Thompson & D. Barford (2010b). The APC/C subunit Cdc16/Cut9 is a contiguous tetratricopeptide repeat superhelix with a homo-dimer interface similar to Cdc27. The Embo Journal 29, 37333744.

N. Zheng , B. A. Schulman , L. Song , J. J. Miller , P. D. Jeffrey , P. Wang , C. Chu , D. M. Koepp , S. J. Elledge , M. Pagano , R. C. Conaway , J. W. Conaway , J. W. Harper & N. P. Pavletich (2002). Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex. Nature 416, 703709.

N. Zheng , P. Wang , P. D. Jeffrey & N. P. Pavletich (2000). Structure of a c-Cbl-UbcH7 complex: RING domain function in ubiquitin-protein ligases. Cell 102, 533539.

A. Zur & M. Brandeis (2002). Timing of APC/C substrate degradation is determined by fzy/fzr specificity of destruction boxes. Embo Journal 21, 45004510.

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Quarterly Reviews of Biophysics
  • ISSN: 0033-5835
  • EISSN: 1469-8994
  • URL: /core/journals/quarterly-reviews-of-biophysics
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