| Regulation of mouse SP-B gene promoter by AP-1 family members. | |
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MedLine Citation:
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PMID: 10409233 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Z Sever-Chroneos; C J Bachurski; C Yan; J A Whitsett |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of physiology Volume: 277 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1999 Jul |
Date Detail:
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Created Date: 1999-08-18 Completed Date: 1999-08-18 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: L79-88 Citation Subset: IM |
Affiliation:
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Division of Pulmonary Biology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Base Sequence / genetics Binding Sites / physiology Mice 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 | |
ID/Acronym/Agency:
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HL-38859/HL/NHLBI NIH HHS; HL-56387/HL/NHLBI NIH HHS; HL-60907/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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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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