Cis-regulation of the L-type pyruvate kinase gene promoter by glucose, insulin and cyclic AMP

Nucleic Acids Res. 1992 Apr 25;20(8):1871-7. doi: 10.1093/nar/20.8.1871.

Abstract

The glucose/insulin response element of the L-pyruvate kinase gene is a perfect palindrome located from nt -168 to -144 with respect to the cap site. This element (L4) is partially homologous to MLTF binding sites. Its full efficiency requires cooperation with a contiguous binding site for HNF4, termed L3 and located from nt -145 to -125. In the presence of the L4 element contiguous to L3, cyclic AMP inhibits activity of the L-PK promoter while in its absence, or when the normal L4-L3 contiguity is modified, cyclic AMP behaves as a transcriptional activator that does not seem to be sequence-specific. Therefore, we propose that the mechanism of inhibition of the L-PK gene by cyclic AMP requires precise interactions between the nucleoprotein complex built up at sites L4 and L3 and other components of the L-PK transcription initiation complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • Cyclic AMP / pharmacology*
  • Gene Expression Regulation, Enzymologic / drug effects
  • Glucose / pharmacology*
  • Insulin / pharmacology*
  • Male
  • Molecular Sequence Data
  • Promoter Regions, Genetic / genetics*
  • Pyruvate Kinase / genetics*
  • Rats
  • Rats, Inbred Strains
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Repetitive Sequences, Nucleic Acid / genetics

Substances

  • Insulin
  • Recombinant Fusion Proteins
  • Cyclic AMP
  • Pyruvate Kinase
  • Glucose