Document Detail


APC/C-mediated degradation in early mitosis: how to avoid spindle assembly checkpoint inhibition.
MedLine Citation:
PMID:  16861901     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The APC/C is an E3 ubiquitin ligase that, by targeting substrates for proteasomal degradation, plays a major role in cell cycle control. In complex with one of two WD40 activator proteins, Cdc20 or Cdh1, the APC/C is active from early mitosis through to late G1 and during this time targets many critical regulators of the cell cycle for degradation. However, this destruction is carefully ordered to ensure that cell cycle events are executed in a timely fashion. Recent studies have begun to shed light on how the APC/C selects different substrates at different times in the cell cycle. One particular problem is how the APC/C recognizes its first set of substrates, Nek2A and cyclin A, in early mitosis when, at this time, the spindle assembly checkpoint (SAC) inhibits most APC/C-dependent degradation. The answer may lie in how substrates are recruited to the APC/C. While checkpoint-dependent substrates appear to require Cdc20 for recruitment, experiments on the early mitotic substrate Nek2A demonstrate that it can bind the APC/C in the absence of Cdc20. The direct interaction of substrates with core subunits of the APC/C could allow their degradation to proceed unhindered even when the SAC is active.
Authors:
Andrew M Fry; Hiroyuki Yamano
Publication Detail:
Type:  Journal Article; Review     Date:  2006-07-17
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  5     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-08-02     Completed Date:  2006-10-04     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1487-91     Citation Subset:  IM    
Affiliation:
Department of Biochemistry, University of Leicester, Leicester, UK. amf5@le.ac.uk
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MeSH Terms
Descriptor/Qualifier:
Animals
Cyclins / metabolism*
Endopeptidases / metabolism
Humans
Mitosis*
Mitotic Spindle Apparatus
Ubiquitin-Protein Ligase Complexes / metabolism*
Ubiquitin-Protein Ligases / metabolism
Chemical
Reg. No./Substance:
0/Cyclins; EC 3.4.-/Endopeptidases; EC 6.3.2.19/Ubiquitin-Protein Ligase Complexes; EC 6.3.2.19/Ubiquitin-Protein Ligases; EC 6.3.2.19/anaphase-promoting complex

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


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