Document Detail


c-Myb promotes the survival of CD4+CD8+ double-positive thymocytes through upregulation of Bcl-xL.
MedLine Citation:
PMID:  20142358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mechanisms that regulate the lifespan of CD4(+)CD8(+) double-positive (DP) thymocytes help shape the peripheral T cell repertoire. However, the molecular mechanisms controlling DP thymocyte survival remain poorly understood. The Myb proto-oncogene encodes a transcription factor required during multiple stages of T cell development. We demonstrate that Myb mRNA expression is upregulated as thymocytes differentiate from the double-negative into the metabolically quiescent, small, preselection DP stage during T cell development. Using a conditional deletion mouse model, we demonstrate that Myb-deficient DP thymocytes undergo premature apoptosis, resulting in a limited Tcralpha repertoire biased toward 5' Jalpha segment usage. Premature apoptosis occurs specifically in the small preselection DP compartment in an alphabetaTCR-independent manner and is a consequence of decreased Bcl-xL expression. Forced Bcl-xL expression is able to rescue survival, and reintroduction of c-Myb restores both Bcl-xL expression and the small preselection DP compartment. We further demonstrate that c-Myb promotes transcription at the Bcl2l1 locus via a genetic pathway that is independent of the expression of T cell-specific factor-1 or RORgammat, two transcription factors that induce Bcl-xL expression in T cell development. Thus, Bcl-xL is a novel mediator of c-Myb activity during normal T cell development.
Authors:
Joan Yuan; Rowena B Crittenden; Timothy P Bender
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-08
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  184     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-04     Completed Date:  2010-05-03     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2793-804     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
GEO/GSE19528
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MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD4 / biosynthesis*,  genetics
Antigens, CD8 / biosynthesis*,  genetics
Apoptosis / genetics,  immunology
Cell Differentiation / genetics,  immunology
Cell Survival / genetics,  immunology
Clone Cells
Coculture Techniques
Integrases / biosynthesis,  genetics
Mice
Mice, Knockout
Mice, Transgenic
Proto-Oncogene Proteins c-myb / deficiency,  genetics,  physiology*
T-Lymphocyte Subsets / cytology,  immunology,  metabolism
Thymus Gland / cytology,  immunology*,  metabolism*
Up-Regulation / genetics,  immunology*
bcl-X Protein / biosynthesis*,  genetics,  physiology
Grant Support
ID/Acronym/Agency:
CA85842/CA/NCI NIH HHS; F06 TW002297/TW/FIC NIH HHS; F06 TW002297-01/TW/FIC NIH HHS; R01 CA085842/CA/NCI NIH HHS; R01 CA085842-08/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD4; 0/Antigens, CD8; 0/Bcl2l1 protein, mouse; 0/Proto-Oncogene Proteins c-myb; 0/bcl-X Protein; EC 2.7.7.-/Cre recombinase; EC 2.7.7.-/Integrases
Comments/Corrections

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


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