Document Detail

Regulation of mouse SP-B gene promoter by AP-1 family members.
MedLine Citation:
PMID:  10409233     Owner:  NLM     Status:  MEDLINE    
The regulatory role of activator protein-1 (AP-1) family members in mouse surfactant protein (SP) B (mSP-B) promoter function was assessed in the mouse lung epithelial cell line MLE-15. Expression of recombinant Jun B and c-Jun inhibited mSP-B promoter activity by 50-75%. Although c-Fos expression did not alter mSP-B transcription, Jun D enhanced mSP-B promoter activity and reversed inhibition of mSP-B by c-Jun or Jun B. A proximal AP-1 binding site (-18 to -10 bp) was identified that overlaps a thyroid transcription factor-1 binding site. Mutation of this proximal AP-1 site blocked both Jun B inhibition and Jun D enhancement and partially blocked c-Jun inhibition of promoter activity. Promoter deletion mutants were used to identify additional sequences mediating the inhibitory effects of c-Jun in the distal region from -397 to -253 bp. The AP-1 element in this distal site (-370 to -364 bp) is part of a composite binding site wherein AP-1, cAMP response element binding protein, thyroid transcription factor-1, and nuclear factor I interact. Point mutation of the distal AP-1 binding site partially blocked c-Jun-mediated inhibition of the SP-B promoter. Both stimulatory (Jun D) and inhibitory (c-Jun/Jun B) effects of AP-1 family members on mSP-B promoter activity are mediated by distinct cis-acting elements in the mSP-B 5'-flanking region.
Z Sever-Chroneos; C J Bachurski; C Yan; J A Whitsett
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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:  The American journal of physiology     Volume:  277     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-08-18     Completed Date:  1999-08-18     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  L79-88     Citation Subset:  IM    
Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
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MeSH Terms
Base Sequence / genetics
Binding Sites / physiology
Molecular Sequence Data
Multigene Family / physiology*
Nuclear Proteins / metabolism
Promoter Regions, Genetic / physiology*
Proteolipids / genetics*
Proto-Oncogene Proteins c-jun / genetics,  physiology
Pulmonary Surfactants / genetics*
Transcription Factor AP-1 / genetics*,  metabolism
Transcription Factors / metabolism
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Nuclear Proteins; 0/Proteolipids; 0/Proto-Oncogene Proteins c-jun; 0/Pulmonary Surfactants; 0/Transcription Factor AP-1; 0/Transcription Factors; 0/thyroid nuclear factor 1

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