Document Detail

Suppression of apoptosis by dominant negative mutants of cyclin-dependent protein kinases.
MedLine Citation:
PMID:  8626584     Owner:  NLM     Status:  MEDLINE    
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.
W Meikrantz; R Schlegel
Related Documents :
21254334 - Forced involution of the functionally differentiated mammary gland by overexpression of...
16652154 - Telomerase inhibition with a novel g-quadruplex-interactive agent, telomestatin: in vit...
20605144 - Romidepsin reduces histone deacetylase activity, induces acetylation of histones, inhib...
19609944 - Tissue inhibitor of metalloproteinase-1 protects mcf-7 breast cancer cells from paclita...
25444914 - Synergistic antitumor activity of withaferin a combined with oxaliplatin triggers react...
8354204 - Studies with 1,2-dithiole-3-thione as a chemoprotector of hydroquinone-induced toxicity...
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    
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Alkaloids / pharmacology
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
Protein-Serine-Threonine Kinases / physiology*
Proto-Oncogene Proteins / physiology
Proto-Oncogene Proteins c-bcl-2
Tumor Necrosis Factor-alpha / pharmacology
Grant Support
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 Kinases; EC Kinases; EC protein, human; EC protein, human; EC protein, human; EC Kinase 2; EC Kinase 3; EC Kinase 5; EC Kinases

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

Previous Document:  Insulin-mediated targeting of phosphatidylinositol 3-kinase to GLUT4-containing vesicles.
Next Document:  Identification of a new outwardly rectifying Cl- channel that belongs to a subfamily of the ClC Cl- ...