Document Detail

Inhibitory phosphorylation of cyclin-dependent kinase 1 as a compensatory mechanism for mitosis exit.
MedLine Citation:
PMID:  21262764     Owner:  NLM     Status:  MEDLINE    
The current paradigm states that exit from mitosis is triggered by the ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) acting in concert with an activator called CDC20. While this has been well established for a number of systems, the evidence of a critical role of CDC20 in somatic cells is not unequivocal. In this study, we reexamined whether mitotic exit can occur properly after CDC20 is depleted. Using single-cell analysis, we found that CDC20 depletion with small interfering RNAs (siRNAs) significantly impaired the degradation of APC/C substrates and delayed mitotic exit in various cancer cell lines. The recruitment of cyclin B1 to the core APC/C was defective after CDC20 downregulation. Nevertheless, CDC20-depleted cells were still able to complete mitosis, albeit requiring twice the normal time. Intriguingly, a high level of cyclin-dependent kinase 1 (CDK1)-inhibitory phosphorylation was induced during mitotic exit in CDC20-depleted cells. The expression of an siRNA-resistant CDC20 rescued both the mitotic exit delay and the CDK1-inhibitory phosphorylation. Moreover, the expression of a nonphosphorylatable CDK1 mutant or the downregulation of WEE1 and MYT1 abolished mitotic exit in CDC20-depleted cells. These findings indicate that, in the absence of sufficient APC/C activity, an alternative mechanism that utilized the classic inhibitory phosphorylation of CDK1 could mediate mitotic exit.
Jeremy P H Chow; Randy Y C Poon; Hoi Tang Ma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-01-24
Journal Detail:
Title:  Molecular and cellular biology     Volume:  31     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-17     Completed Date:  2011-05-16     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1478-91     Citation Subset:  IM    
Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong.
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MeSH Terms
CDC2 Protein Kinase / antagonists & inhibitors*,  metabolism
Cell Cycle Proteins / metabolism
Cyclin B1 / metabolism
DNA-Binding Proteins / metabolism
HeLa Cells
Nuclear Proteins / metabolism
Protein Processing, Post-Translational
Protein-Tyrosine Kinases / metabolism
Substrate Specificity
Time-Lapse Imaging
Transcription Factors / metabolism
Ubiquitin-Protein Ligase Complexes / metabolism
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Cyclin B1; 0/DNA-Binding Proteins; 0/MYT1 protein, human; 0/Nuclear Proteins; 0/Transcription Factors; 156288-95-8/CDC20 protein, human; EC Kinases; EC protein, human; EC Protein Kinase; EC Ligase Complexes; EC complex

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