Document Detail


G0 function of BCL2 and BCL-xL requires BAX, BAK, and p27 phosphorylation by Mirk, revealing a novel role of BAX and BAK in quiescence regulation.
MedLine Citation:
PMID:  18818203     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BCL2 and BCL-x(L) facilitate G(0) quiescence by decreasing RNA content and cell size and up-regulating p27 protein, but the precise mechanism is not understood. We investigated the relationship between cell cycle regulation and the anti-apoptosis function of BCL2 and BCL-x(L). Neither caspase inhibition nor abrogation of mitochondria-dependent apoptosis by BAX and BAK deletion fully recapitulated the G(0) effects of BCL2 or BCL-x(L), suggesting that mechanisms in addition to anti-apoptosis are involved in the cell cycle arrest function of BCL2 or BCL-x(L). We found that BCL2 and BCL-x(L) expression in bax(-/-) bak(-/-) cells did not confer cell cycle effects, consistent with the G(0) function of BCL2 and BCL-x(L) being mediated through BAX or BAK. Stabilization of p27 in G(0) in BCL2 or BCL-x(L) cells was due to phosphorylation of p27 at Ser(10) by the kinase Mirk. In bax(-/-) bak(-/-) cells, total p27 and p27 phosphorylated at Ser(10) were elevated. Re-expression of BAX in bax(-/-) bak(-/-) cells and silencing of BAX and BAK in wild type cells confirmed that endogenous BAX and BAK modulated p27. These data revealed a novel role for BAX and BAK in the regulation of G(0) quiescence.
Authors:
Yelena Janumyan; Qinghua Cui; Ling Yan; Courtney G Sansam; Mayda Valentin; Elizabeth Yang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-09-25
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-01     Completed Date:  2009-02-04     Revised Date:  2010-09-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  34108-20     Citation Subset:  IM    
Affiliation:
Department of Pediatrics, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Caspase 9 / metabolism
Cell Cycle
Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
Enzyme Inhibitors / pharmacology
Gene Expression Regulation, Enzymologic*
Humans
Mice
Models, Biological
Mutation
Protein-Serine-Threonine Kinases / physiology*
Protein-Tyrosine Kinases / physiology*
Proto-Oncogene Proteins c-bcl-2 / physiology*
Rats
bcl-2 Homologous Antagonist-Killer Protein / physiology*
bcl-2-Associated X Protein / physiology*
bcl-X Protein / metabolism*
Grant Support
ID/Acronym/Agency:
R01CA78443/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins c-bcl-2; 0/bcl-2 Homologous Antagonist-Killer Protein; 0/bcl-2-Associated X Protein; 0/bcl-X Protein; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27; EC 2.7.1.-/Dyrk kinase; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 3.4.22.-/Caspase 9
Comments/Corrections

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