Transcription factor NF1 mediates repression of the GLUT4 promoter by cyclic-AMP

David W. Cooke, M. Daniel Lane

Research output: Contribution to journalArticlepeer-review

Abstract

Prolonged treatment of 3T3-L1 adipocytes with 8-Br-cAMP decreases expression of GLUT4, the insulin-responsive glucose transporter. Expression of a promoter-reporter gene construct that contained 785 base pairs of 5'-flanking region of the murine GLUT4 gene was down regulated by 8-Br-cAMP (p < 0.001), whereas expression of constructs that contained 641 or 469 base pairs of 5'-flanking region was not. A reporter gene construct in which bases -706 to -676 were deleted was not repressed by 8-Br-cAMP, thereby identifying a 30 bp region as necessary for repression of the GLUT4 promoter by 8-Br-cAMP. Mutations in this regulatory element that disrupt binding of the transcription factor NF1 abolish the 8-Br-cAMP-induced repression of the gene. Although insulin and cAMP both repress the GLUT4 promoter through this cis-element, they appear to do this through different mechanisms, as treatment with 8-Br-cAMP does not induce the phosphorylation of NF1 that is induced by insulin treatment.

Original languageEnglish (US)
Pages (from-to)600-604
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume260
Issue number3
DOIs
StatePublished - Jul 14 1999

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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