Document Detail

Induction of the RelB NF-kappaB subunit by the cytomegalovirus IE1 protein is mediated via Jun kinase and c-Jun/Fra-2 AP-1 complexes.
MedLine Citation:
PMID:  15596805     Owner:  NLM     Status:  MEDLINE    
We recently demonstrated that the cytomegalovirus (CMV) immediate-early 1 (IE1) protein induces transcription of the gene encoding the RelB NF-kappaB subunit. The mechanism of this activation has been explored here. We report that the induction of the relB promoter by IE1 protein is mediated via activation of JNK and AP-1. The region controlling relB promoter induction was mapped to the upstream approximately 600-bp region between -1694 and -1096 bp. IE1 stimulated AP-1 activity in NIH 3T3 cells. Competition electrophoretic mobility shift assay (EMSA) confirmed the presence of one bona fide AP-1 element centered at -1503 bp. Introduction of a G-to-C mutation in the AP-1 binding site within the distal region of the relB promoter eliminated its activation by IE1 in both NIH 3T3 fibroblasts and vascular smooth muscle cells (SMCs). Supershift EMSA identified c-Jun, Fra-2, and c-Fos in AP-1 binding complexes in IE1 transfected NIH 3T3 cells. IE1 induced c-Jun phosphorylation, and treatment with SP600125, a selective JNK inhibitor, as well as overexpression of JNK-binding domain of JIP1, blocked IE1-mediated induction of AP-1 and relB promoter activity in NIH 3T3 cells and SMCs. Ectopic expression of c-Jun plus Fra-2, but not c-Fos, induced relB promoter activity. The relB promoter has two proximal NF-kappaB elements, and c-Jun/Fra-2 worked in synergy with p50/p65 NF-kappaB complexes. Overall, these findings demonstrate for the first time the role of AP-1 in transcriptional regulation of a gene encoding an NF-kappaB subunit, and its involvement in induction of RelB activity by the CMV IE1 protein.
Xiaobo Wang; Gail E Sonenshein
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of virology     Volume:  79     ISSN:  0022-538X     ISO Abbreviation:  J. Virol.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2004-12-14     Completed Date:  2005-01-14     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  95-105     Citation Subset:  IM    
Department of Biochemistry, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
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MeSH Terms
DNA-Binding Proteins / genetics,  metabolism
Fos-Related Antigen-2
Gene Expression Regulation*
Immediate-Early Proteins / genetics,  metabolism*
JNK Mitogen-Activated Protein Kinases / genetics,  metabolism
Mutagenesis, Site-Directed
NF-kappa B / genetics,  metabolism
NIH 3T3 Cells
Promoter Regions, Genetic
Proto-Oncogene Proteins / genetics,  metabolism*
Proto-Oncogene Proteins c-jun / genetics,  metabolism
Transcription Factor AP-1 / genetics,  metabolism*
Transcription Factor RelB
Transcription Factors / genetics,  metabolism*
Transcription, Genetic*
Viral Proteins / genetics,  metabolism*
Grant Support
Reg. No./Substance:
0/DNA-Binding Proteins; 0/FOSL2 protein, human; 0/Fos-Related Antigen-2; 0/Fosl2 protein, mouse; 0/IE1 protein, cytomegalovirus; 0/Immediate-Early Proteins; 0/NF-kappa B; 0/Proto-Oncogene Proteins; 0/Proto-Oncogene Proteins c-jun; 0/RELB protein, human; 0/Relb protein, mouse; 0/Transcription Factor AP-1; 0/Transcription Factors; 0/Viral Proteins; 147337-75-5/Transcription Factor RelB; EC Mitogen-Activated Protein Kinases

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