Document Detail


Bcl-2 inhibition of T-cell proliferation is related to prolonged T-cell survival.
MedLine Citation:
PMID:  15034548     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Bcl-2 promotes oncogenesis by inhibiting cell death. Bcl-2 also inhibits proliferation and suppresses tumorigenesis in some settings. To clarify the role of the antiproliferative function of Bcl-2, mice expressing a mutant form of Bcl-2 reported to lack antiproliferative activity were generated (tyrosine 28 to alanine, Bcl-2-Y28A). As expected, both wild type (WT) and Bcl-2-Y28A inhibited apoptosis similarly. In contrast to previous results in cell lines, Bcl-2-Y28A inhibited T-cell proliferation identical to WT-Bcl-2. Significantly, both Bcl-2-Y28A and WT-Bcl-2 inhibited proliferation of T cells isolated from older animals, but not proliferation of T cells from immature mice. Instead, inhibition of cell activation correlated with T-cell size, p27 levels, and RNA content, all indicators of quiescent G0 arrest. Consistent with this model, Bcl-2 inhibition of T-cell proliferation was reversed by expression of Bax, again correlating cell proliferation with cell size. These experiments do not support genetically separate effects of Bcl-2 on apoptosis and proliferation. Instead, the data support a model in which Bcl-2 and Bax regulate T-cell proliferation by changes in T-cell size and by increasing the markers of quiescent G0 arrest. These changes likely result from prolonged T-cell survival.
Authors:
Ningli Cheng; Yelena M Janumyan; Lisa Didion; Chris Van Hofwegen; Elizabeth Yang; C Michael Knudson
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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:  Oncogene     Volume:  23     ISSN:  0950-9232     ISO Abbreviation:  Oncogene     Publication Date:  2004 May 
Date Detail:
Created Date:  2004-05-06     Completed Date:  2004-05-20     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8711562     Medline TA:  Oncogene     Country:  England    
Other Details:
Languages:  eng     Pagination:  3770-80     Citation Subset:  IM    
Affiliation:
Department of Pathology, The University of Iowa Roy J and Lucille P Carver College of Medicine, 3160 ML, Iowa City, IA 52242, USA.
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Animals
Apoptosis*
Cell Cycle
Cell Survival
Lymphocyte Activation*
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / physiology
Mice
Mice, Transgenic
Microfilament Proteins / analysis
Muscle Proteins*
Proto-Oncogene Proteins / physiology
Proto-Oncogene Proteins c-bcl-2 / physiology
Pyronine / analysis
T-Lymphocytes / immunology*,  physiology
bcl-2-Associated X Protein
Grant Support
ID/Acronym/Agency:
1R01CA78443/CA/NCI NIH HHS; 1R01CA88967/CA/NCI NIH HHS; T32GM08554/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Bax protein, mouse; 0/Microfilament Proteins; 0/Muscle Proteins; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-bcl-2; 0/Tagln protein, mouse; 0/bcl-2-Associated X Protein; 92-32-0/Pyronine; EC 2.7.10.2/Lymphocyte Specific Protein Tyrosine Kinase p56(lck)

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


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