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Cdk1-phosphorylated CUEDC2 promotes spindle checkpoint inactivation and chromosomal instability.
MedLine Citation:
PMID:  21743465     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Aneuploidy and chromosomal instability are major characteristics of human cancer. These abnormalities can result from defects in the spindle assembly checkpoint (SAC), which is a surveillance mechanism for accurate chromosome segregation through restraint of the activity of the anaphase-promoting complex/cyclosome (APC/C). Here, we show that a CUE-domain-containing protein, CUEDC2, is a cell-cycle regulator that promotes spindle checkpoint inactivation and releases APC/C from checkpoint inhibition. CUEDC2 is phosphorylated by Cdk1 during mitosis. Depletion of CUEDC2 causes a checkpoint-dependent delay of the metaphase-anaphase transition. Phosphorylated CUEDC2 binds to Cdc20, an activator of APC/C, and promotes the release of Mad2 from APC/C-Cdc20 and subsequent APC/C activation. CUEDC2 overexpression causes earlier activation of APC/C, leading to chromosome missegregation and aneuploidy. Interestingly, CUEDC2 is highly expressed in many types of tumours. These results suggest that CUEDC2 is a key regulator of mitosis progression, and that CUEDC2 dysregulation might contribute to tumour development by causing chromosomal instability.
Authors:
Yan-Fei Gao; Teng Li; Yan Chang; Yu-Bo Wang; Wei-Na Zhang; Wei-Hua Li; Kun He; Rui Mu; Cheng Zhen; Jiang-Hong Man; Xin Pan; Tao Li; Liang Chen; Ming Yu; Bing Liang; Yuan Chen; Qing Xia; Tao Zhou; Wei-Li Gong; Ai-Ling Li; Hui-Yan Li; Xue-Min Zhang
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-7-10
Journal Detail:
Title:  Nature cell biology     Volume:  -     ISSN:  1476-4679     ISO Abbreviation:  -     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-7-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100890575     Medline TA:  Nat Cell Biol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1] Institute of Basic Medical Sciences, National Center of Biomedical Analysis, 27 Tai-Ping Road, Beijing 100850, China [2].
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