Document Detail

CD28-mediated regulation of the c-jun promoter involves the MEF2 transcription factor in Jurkat T cells.
MedLine Citation:
PMID:  10403485     Owner:  NLM     Status:  MEDLINE    
Within a few minutes of T-cell activation, transcription of a set of genes including c-fos and c-jun is activated. For maximal induction of c-jun, at least two major signal pathways are required. One can be triggered by T-cell receptor engagement or phorbol esters and the other by anti-CD28 engagement. The c-jun promoter region between -117 and -50 contains binding sites for the transcription factors Spl, CTF, ATF/CREB, and MEF2. In this study, we sought to map the sequences in the c-jun promoter responsible for CD28-mediated induction in activated Jurkat T cell by point mutational analysis. We found that mutation of the c-jun MEF2 site strongly reduces CD28 induction of the promoter in Jurkat T cells and that MEF2D is the major binding molecule to the c-jun MEF2 site in Jurkat T cells. Mutation of the c-jun ATF site also partially reduced CD28 induction of the promoter. In addition, pretreatment with an endolysomotropic agent NH4Cl, an acidic sphingomyelinase inhibitor, completely inhibited the activation of the c-jun promoter by anti-CD28 antibody treatment, whereas pretreatment with wortmannin, a PI3-kinase inhibitor, did not affect the induction of the c-jun promoter. These results suggest that CD28 signaling leading to the c-jun promoter involves acidic sphingomyelinase, but not PI3-kinase, to activate factors binding to the MEF2 and ATF sites.
H M Shin; T H Han
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular immunology     Volume:  36     ISSN:  0161-5890     ISO Abbreviation:  Mol. Immunol.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-07-20     Completed Date:  1999-07-20     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  7905289     Medline TA:  Mol Immunol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  197-203     Citation Subset:  IM    
Department of Microbiology and Immunology, Sungkyunkwan University School of Medicine, Suwon, South Korea.
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MeSH Terms
1-Phosphatidylinositol 3-Kinase / physiology
Antigens, CD28 / physiology*
Binding Sites / genetics
DNA-Binding Proteins / physiology*
Gene Expression Regulation / immunology*
Genes, jun / immunology*
Jurkat Cells / immunology,  metabolism*
MADS Domain Proteins
Myogenic Regulatory Factors
Promoter Regions, Genetic / immunology*
Regulatory Sequences, Nucleic Acid / genetics
Signal Transduction / immunology
Sphingomyelin Phosphodiesterase / physiology
Transcription Factors / physiology*
Reg. No./Substance:
0/Antigens, CD28; 0/DNA-Binding Proteins; 0/MADS Domain Proteins; 0/MEF2D protein, human; 0/Myogenic Regulatory Factors; 0/Transcription Factors; 0/myocyte-specific enhancer-binding factor 2; EC 3-Kinase; EC Phosphodiesterase

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