Unsaturated fatty acids as high-affinity ligands of the C-terminal Per-ARNT-Sim domain from the Hypoxia-inducible factor 3α

Sci Rep. 2015 Aug 3:5:12698. doi: 10.1038/srep12698.

Abstract

Hypoxia-inducible transcription factors (HIF) form heterodimeric complexes that mediate cell responses to hypoxia. The oxygen-dependent stability and activity of the HIF-α subunits is traditionally associated to post-translational modifications such as hydroxylation, acetylation, ubiquitination, and phosphorylation. Here we report novel evidence showing that unsaturated fatty acids are naturally occurring, non-covalent structural ligands of HIF-3α, thus providing the initial framework for exploring its exceptional role as a lipid sensor under hypoxia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins
  • Basic Helix-Loop-Helix Transcription Factors / chemistry
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Humans
  • Ligands
  • Linoleic Acid / chemistry
  • Linoleic Acid / metabolism*
  • Models, Molecular
  • Monoglycerides / chemistry
  • Monoglycerides / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Oleic Acid / chemistry
  • Oleic Acid / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Repressor Proteins
  • Signal Transduction
  • Stearic Acids / chemistry
  • Stearic Acids / metabolism
  • Tissue Array Analysis

Substances

  • Apoptosis Regulatory Proteins
  • Basic Helix-Loop-Helix Transcription Factors
  • HIF3A protein, human
  • Ligands
  • Monoglycerides
  • Recombinant Proteins
  • Repressor Proteins
  • Stearic Acids
  • Oleic Acid
  • stearic acid
  • Linoleic Acid