Document Detail


Cyclin A/Cdk2 regulates Cdh1 and claspin during late S/G2 phase of the cell cycle.
MedLine Citation:
PMID:  25485510     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Whereas many components regulating the progression from S phase through G2 phase into mitosis have been identified, the mechanism by which these components control this critical cell cycle progression is still not fully elucidated. Cyclin A/Cdk2 has been shown to regulate the timing of Cyclin B/Cdk1 activation and progression into mitosis although the mechanism by which this occurs is only poorly understood. Here we show that depletion of Cyclin A or inhibition of Cdk2 during late S/early G2 phase maintains the G2 phase arrest by reducing Cdh1 transcript and protein levels, thereby stabilizing Claspin and maintaining elevated levels of activated Chk1 which contributes to the G2 phase observed. Interestingly, the Cyclin A/Cdk2 regulated APC/C(Cdh1) activity is selective for only a subset of Cdh1 targets including Claspin. Thus, a normal role for Cyclin A/Cdk2 during early G2 phase is to increase the level of Cdh1 which destabilises Claspin which in turn down regulates Chk1 activation to allow progression into mitosis. This mechanism links S phase exit with G2 phase transit into mitosis, provides a novel insight into the roles of Cyclin A/Cdk2 in G2 phase progression, and identifies a novel role for APC/C(Cdh1) in late S/G2 phase cell cycle progression.
Authors:
Vanessa Oakes; Weili Wang; Brittney Harrington; Won Jae Lee; Heather Beamish; Kee Ming Chia; Alex Pinder; Hidemasa Goto; Masaki Inagaki; Sandra Pavey; Brian Gabrielli
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Cell cycle (Georgetown, Tex.)     Volume:  13     ISSN:  1551-4005     ISO Abbreviation:  Cell Cycle     Publication Date:  2014 Oct 
Date Detail:
Created Date:  2014-12-09     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101137841     Medline TA:  Cell Cycle     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3302-11     Citation Subset:  IM    
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