Document Detail


Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases.
MedLine Citation:
PMID:  8626584     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In many cell types, position in the cell cycle appears to play a role in determining susceptibility to apoptosis (programmed cell death), and expression of various cyclins and activation of cyclin-dependent kinases (CDKs) have been shown to correlate with the onset of apoptosis in a number of experimental systems. To assess the role of CDK-mediated cell cycle events in apoptosis, we have expressed CDK dominant negative mutants in human HeLa cells. Dominant negative mutants of CDC2, CDK2, and CDK3 each suppressed apoptosis induced by both staurosporine and tumor necrosis factor alpha, whereas a dominant negative mutant of CDK5 was without effect. Like CDC2 and CDK2, CDK3 was shown to form a complex with cyclin A in vivo. CDK5 did not bind cyclin A to any detectable extent. Overexpression of wild type CDC2, CDK2, CDK3, or cyclin A (but not cyclin B) markedly elevated the incidence of apoptosis in BCL-2+ cells, which otherwise fail to respond to these agents. These results help identify cell cycle events that are also important for efficient apoptosis.
Authors:
W Meikrantz; R Schlegel
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  271     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1996 Apr 
Date Detail:
Created Date:  1996-06-21     Completed Date:  1996-06-21     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  10205-9     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
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MeSH Terms
Descriptor/Qualifier:
Alkaloids / pharmacology
Apoptosis*
CDC2-CDC28 Kinases*
Cyclin-Dependent Kinase 2
Cyclin-Dependent Kinase 3
Cyclin-Dependent Kinase 5
Cyclin-Dependent Kinases / physiology*
Cyclins / physiology
Cycloheximide / pharmacology
Genes, Dominant
HeLa Cells
Humans
Protein-Serine-Threonine Kinases / physiology*
Proto-Oncogene Proteins / physiology
Proto-Oncogene Proteins c-bcl-2
Staurosporine
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
ID/Acronym/Agency:
CA61626/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Alkaloids; 0/Cyclins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tumor Necrosis Factor-alpha; 62996-74-1/Staurosporine; 66-81-9/Cycloheximide; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.22/CDC2-CDC28 Kinases; EC 2.7.11.22/CDK2 protein, human; EC 2.7.11.22/CDK3 protein, human; EC 2.7.11.22/CDK5 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 2; EC 2.7.11.22/Cyclin-Dependent Kinase 3; EC 2.7.11.22/Cyclin-Dependent Kinase 5; EC 2.7.11.22/Cyclin-Dependent Kinases

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


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