Document Detail


Coactivator functions in a stoichiometric complex with anaphase-promoting complex/cyclosome to mediate substrate recognition.
MedLine Citation:
PMID:  16113654     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The anaphase-promoting complex/cyclosome (APC/C) is a multisubunit E3 ligase required for ubiquitin-dependent proteolysis of cell-cycle-regulatory proteins, including mitotic cyclins and securin/Pds1. Regulation of APC/C activity and substrate recognition, mediated by the coactivators Cdc20 and Cdh1, is fundamental to cell-cycle control. However, the precise mechanism by which coactivators stimulate APC/C ubiquitylation activity and the nature of the substrate-binding sites on the activated APC/C are not understood. Here, we show that the optimal interaction of substrate with APC/C is dependent specifically on the simultaneous association of coactivator. This is consistent with a model whereby both core APC/C subunits and coactivators contribute recognition sites for substrates, accounting for the bipartite nature (D and KEN boxes) of most APC/C degradation signals. A direct and stoichiometric function for the coactivators could explain how specific substrates are recognized by APC/C in a cell-cycle-specific manner, and how coactivator stimulates APC/C ubiquitylation activity.
Authors:
Lori A Passmore; David Barford
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  EMBO reports     Volume:  6     ISSN:  1469-221X     ISO Abbreviation:  EMBO Rep.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-09-02     Completed Date:  2006-03-28     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  100963049     Medline TA:  EMBO Rep     Country:  England    
Other Details:
Languages:  eng     Pagination:  873-8     Citation Subset:  IM    
Affiliation:
Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
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MeSH Terms
Descriptor/Qualifier:
Cell Cycle / physiology*
Cell Cycle Proteins / metabolism*
Electrophoresis, Polyacrylamide Gel
Models, Biological*
Protein Binding
Saccharomyces cerevisiae Proteins / metabolism*
Substrate Specificity
Ubiquitin-Protein Ligase Complexes / metabolism*
Yeasts
Chemical
Reg. No./Substance:
0/CDC20 protein, S cerevisiae; 0/Cell Cycle Proteins; 0/Hct1 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; EC 6.3.2.19/Ubiquitin-Protein Ligase Complexes; EC 6.3.2.19/anaphase-promoting complex
Comments/Corrections

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