Anaphase-Promoting core complex

ComplexAc: CPX-756

Saccharomyces cerevisiae; 559292

Curated by:

IntAct

Components

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ComplexViewer 2.2.4by Rappsilber LaboratoryAPC5CDC16MND2APC1APC4APC2DOC1SWM1CDC23APC11CDC26CDC27APC9tooltip
Legend Description Stoichiometry
protein - MND2 (unspecified role)
Anaphase-promoting complex subunit MND2
protein - DOC1 (unspecified role)
Anaphase-promoting complex subunit DOC1
protein - APC1 (unspecified role)
Anaphase-promoting complex subunit 1
protein - APC11 (enzyme)
Anaphase-promoting complex subunit 11
protein - APC4 (unspecified role)
Anaphase-promoting complex subunit 4
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Function

APC, a key regulator of cell cycle progression, is a conserved cullin-RING E3 ubiqutin ligase which facilitates multiubiqutination of cell cycle proteins, including cyclins, so marking them for proteasomal destruction. Generally believed that APC acts as a scaffold that brings E2 enzymes and substrates into close proximity. APC activity is required for metaphase-anaphase transition, mitotic exit, G1 phase and DNA replication. Targets securin for destruction, which is necessary for chromosome segregation. APC seems to have similar function in meiosis. Co-activators, CDC20 and CDH1, associate with APC core complex at specific stages of cell cycle, and are thought to be involved in substrate specificity. APC-Cdc20 (CPX-760) is active in presence of high cyclin-cdk activity in M phase but after metaphase when cyclin-cdk activity decreases, Cdh1 is dephosphorylated, CDC20 is degraded and APC-CDH1 (CPX-761) activated. Ama1 (CPX-762) is meiotic co-activator required for sporulation and contributes to securin degradation and cyclin Clb5 in anaphase of meiosis. All APC co-activators, characterized by the presence of sequence elements, C-box and the IR-tail, that mediate their binding to APC, contain a C-terminal WD40 domain, predicted to fold into a propeller-like structure, believed to recognize APC substrates by interacting with specific recognition elements in substrates, D-boxes and KEN-boxes. Genetic inactivation of APC is lethal.

Catalytic Activity

EC Numbers (1)

6.3.2.19

Properties

MW = 1.7 MDa. APC is an asymmetric triangular complex (200 by 230 A in size), composed of an outer wall that encloses an internal cavity. The largest APC subunit, APC1, bridges two distinct subcomplexes, the “catalytic core” subcomplex including APC2 and APC11, the Cullin and RING-finger subunits that characterize the APC as a member of the multisubunit cullin-RING family of ubiquitin ligases, and the three TPR subunits CDC27, CDC16, and CDC23, and requires APC4 and APC5 to interact with Apc1. May also exist as a dimer in vivo. Purified APC forms dimers in vitro, which have enhanced processivity.

EMDB Cross References (3)

EMD-1820
EMD-1821
EMD-1822

Expression and Cellular Location

Gene Expression Map

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GO - Cellular Component (1)

anaphase-promoting complex

Additional Information

Further Reading

Identifier Title Author(s)
9695848 Proteolytic ratchets that control progression through mitosis. Townsley FM, Ruderman JV.
15678131 The anaphase-promoting complex: a key factor in the regulation of cell cycle. Castro A, Bernis C, Vigneron S, Labbé JC, Lorca T.
16896351 The anaphase promoting complex/cyclosome: a machine designed to destroy. Peters JM.
16364911 Structural analysis of the anaphase-promoting complex reveals multiple active sites and insights into polyubiquitylation. Passmore LA, Booth CR, Vénien-Bryan C, Ludtke SJ, Fioretto C, Johnson LN, Chiu W, Barford D.
15797379 The yeast APC/C subunit Mnd2 prevents premature sister chromatid separation triggered by the meiosis-specific APC/C-Ama1. Oelschlaegel T, Schwickart M, Matos J, Bogdanova A, Camasses A, Havlis J, Shevchenko A, Zachariae W.
29167309 Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C). Alfieri C, Zhang S, Barford D.

Synonyms (6)

Anaphase-Promoting Complex
Anaphase Promoting Complex/Cyclosome
APC/C
APC
Cyclosome
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Systematic Name

APC1:APC2:APC4:APC5:APC9:APC11:CDC16:CDC23:CDC26:CDC27:DOC1:MND2:SWM1