Document Detail

Growth factor stimulation induces cell survival by c-Jun. ATF2-dependent activation of Bcl-XL.
MedLine Citation:
PMID:  20507983     Owner:  NLM     Status:  MEDLINE    
Growth factor stimulation induces c-Jun-dependent survival of primary endothelial cells. However, the mechanism of c-Jun anti-apoptotic activity has not been identified. We here demonstrate that in response to growth factor treatment, primary human endothelial cells as well as mouse fibroblasts respond with an increased expression of c-Jun that forms a complex with ATF2. This complex activates the expression of the anti-apoptotic protein Bcl-X(L). By site-directed mutagenesis experiments, we identified two AP-1-binding sites located within the proximal promoter of the Bcl-X gene. Site-directed mutagenesis demonstrated that these AP-1 sites are required for the transcriptional activation of the promoter. Chromatin immunoprecipitation experiments show that in response to growth factor treatment, the heterodimer c-Jun.ATF2 binds to these functional AP-1 sites. Silencing of either c-Jun or ATF2 demonstrated that both nuclear factors are required for the activation of the proximal Bcl-X promoter. Taken together, our experiments provide evidence that growth factor-independent signaling pathways converge in the formation of an active c-Jun.AFT2 dimer, which induces the expression of the anti-apoptotic factor Bcl-X(L) that mediates a pro-survival response.
Ahmad Salameh; Federico Galvagni; Francesca Anselmi; Caterina De Clemente; Maurizio Orlandini; Salvatore Oliviero
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-05-27
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  285     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-19     Completed Date:  2010-08-17     Revised Date:  2011-08-01    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  23096-104     Citation Subset:  IM    
Dipartimento di Biologia Molecolare, Universita' di Siena, 53100 Siena, Italy.
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MeSH Terms
Activating Transcription Factor 2 / chemistry,  deficiency,  genetics,  metabolism*
Apoptosis / drug effects
Base Sequence
Binding Sites
Cell Line
Cell Survival / drug effects*
Endothelial Cells / cytology,  drug effects,  metabolism
Fibroblasts / cytology,  drug effects,  metabolism
Gene Expression Regulation / drug effects
Gene Silencing
Intercellular Signaling Peptides and Proteins / pharmacology*
JNK Mitogen-Activated Protein Kinases / chemistry,  deficiency,  genetics,  metabolism*
Protein Multimerization
Protein Structure, Quaternary
Signal Transduction / drug effects
Transcription Factor AP-1 / metabolism
Transcription, Genetic
bcl-X Protein / genetics,  metabolism*
Reg. No./Substance:
0/ATF2 protein, human; 0/Activating Transcription Factor 2; 0/Intercellular Signaling Peptides and Proteins; 0/Transcription Factor AP-1; 0/bcl-X Protein; EC Mitogen-Activated Protein Kinases

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