Regulation of mouse SP-B gene promoter by AP-1 family members

Zvjesdana Sever-Chroneos, Cindy J. Bachurski, Cong Yan, Jeffrey A. Whitsett

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)L79-L88
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume277
Issue number1 21-1
StatePublished - Jul 1 1999

    Fingerprint

Keywords

  • Activator protein-1
  • Gene transcription
  • Pulmonary surfactant
  • Regulatory promoter
  • Respiratory epithelium
  • Surfactant protein B

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this