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    
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.
Lori A Passmore; David Barford
Related Documents :
21736704 - In silico exploration of anti-inflammatory activity of natural coumarinolignoids.
15917634 - Deubiquitinating enzyme purification, assay inhibitors, and characterization.
20688984 - Glutamine deamidation and dysfunction of ubiquitin/nedd8 induced by a bacterial effecto...
22268794 - Measurement and reduction of damping in plasmonic nanowires.
16319224 - Molecular tuning of fast gating in pentameric ligand-gated ion channels.
19523824 - Prolonged stability by cyclization: macrocyclic phosphino dipeptide isostere inhibitors...
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    
Section of Structural Biology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
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*
Reg. No./Substance:
0/CDC20 protein, S cerevisiae; 0/Cell Cycle Proteins; 0/Hct1 protein, S cerevisiae; 0/Saccharomyces cerevisiae Proteins; EC Ligase Complexes; EC complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Ablation of the spindle assembly checkpoint by a compound targeting Mps1.
Next Document:  tRNA-balanced expression of a eukaryal aminoacyl-tRNA synthetase by an mRNA-mediated pathway.