Document Detail


Cdk1/cyclin B1 controls Fas-mediated apoptosis by regulating caspase-8 activity.
MedLine Citation:
PMID:  20937773     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Caspase activation is a hallmark of apoptosis. However, the molecular mechanisms underlying the regulation of caspase-8 activation within the extrinsic death pathway are not well understood. In this study, we demonstrate that procaspase-8 is phosphorylated in mitotic cells by Cdk1/cyclin B1 on Ser-387, which is located at the N terminus of the catalytic subunit p10. This phosphorylation of procaspase-8 on Ser-387 occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. Furthermore, RNA interference-mediated silencing of cyclin B1 or treatment with the Cdk1 inhibitor RO-3306 enhances the Fas-mediated activation and processing of procaspase-8 in mitotic cells. A nonphosphorylatable procaspase-8 (S387A) facilitates Fas-induced apoptosis during mitosis. Our findings suggest that Cdk1/cyclin B1 activity shields human cells against extrinsic death stimuli and unravel the molecular details of the cross talk between cell cycle and extrinsic apoptotic pathways. Finally, this new mechanism may also contribute to tumorigenesis.
Authors:
Yves Matthess; Monika Raab; Mourad Sanhaji; Inna N Lavrik; Klaus Strebhardt
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-11
Journal Detail:
Title:  Molecular and cellular biology     Volume:  30     ISSN:  1098-5549     ISO Abbreviation:  Mol. Cell. Biol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-01-13     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  8109087     Medline TA:  Mol Cell Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5726-40     Citation Subset:  IM    
Affiliation:
Department of Obstetrics and Gynecology, School of Medicine, J W Goethe University, Frankfurt, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD95 / genetics,  metabolism*
Apoptosis / physiology*
Breast Neoplasms / metabolism
CDC2 Protein Kinase / genetics,  metabolism*
Caspase 8 / genetics,  metabolism*
Cell Line
Cyclin B1 / genetics,  metabolism*
Cysteine Proteinase Inhibitors / metabolism
Female
Humans
Leupeptins / metabolism
Recombinant Fusion Proteins / genetics,  metabolism
Signal Transduction / physiology
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Cyclin B1; 0/Cysteine Proteinase Inhibitors; 0/Leupeptins; 0/Recombinant Fusion Proteins; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; EC 2.7.11.22/CDC2 Protein Kinase; EC 3.4.22.-/Caspase 8
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