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

Biochem Biophys Res Commun. 1999 Jul 14;260(3):600-4. doi: 10.1006/bbrc.1999.0959.

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • 8-Bromo Cyclic Adenosine Monophosphate / pharmacology*
  • Adipocytes / cytology
  • Adipocytes / drug effects
  • Animals
  • Base Sequence
  • Colforsin / pharmacology
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / drug effects*
  • Genes, Reporter / genetics
  • Glucose Transporter Type 4
  • Insulin / pharmacology
  • Mice
  • Monosaccharide Transport Proteins / genetics*
  • Muscle Proteins*
  • Mutation
  • NFI Transcription Factors
  • Nuclear Proteins / metabolism
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic / genetics*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Response Elements / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Glucose Transporter Type 4
  • Insulin
  • Monosaccharide Transport Proteins
  • Muscle Proteins
  • NFI Transcription Factors
  • Nuclear Proteins
  • Oligonucleotides
  • RNA, Messenger
  • Slc2a4 protein, mouse
  • Transcription Factors
  • transcription factor nuclear factor 1
  • Colforsin
  • 8-Bromo Cyclic Adenosine Monophosphate