Purified recombinant hARD1 does not catalyse acetylation of Lys532 of HIF-1alpha fragments in vitro

FEBS Lett. 2006 Apr 3;580(8):1911-8. doi: 10.1016/j.febslet.2006.02.012. Epub 2006 Feb 17.

Abstract

In humans, many responses to hypoxia including angiogenesis and erythropoiesis are mediated by the alpha/beta-heterodimeric transcription factor hypoxia inducible factor (HIF). The stability and/or activity of human HIF-1alpha are modulated by post-translational modifications including prolyl and asparaginyl hydroxylation, phosphorylation, and reportedly by acetylation of the side-chain of Lys532 by ARD1 (arrest defective protein 1 homologue), an acetyltransferase. Using purified recombinant human ARD1 (hARD1) we did not observe ARD1-mediated N-acetylation of Lys532 using fragments of HIF-1alpha. However, recombinant hARD1 from Escherichia coli was produced with partial N-terminal acetylation and was observed to undergo slow self-mediated N-terminal acetylation. The observations are consistent with the other data indicating that hARD1, at least alone, does not acetylate HIF-1alpha, and with reports on the N-terminal acetyltransferase activity of a recently reported heterodimeric complex comprising hARD1 and N-acetyltransferase protein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetyltransferases / analysis
  • Acetyltransferases / chemistry
  • Acetyltransferases / isolation & purification*
  • Acetyltransferases / metabolism*
  • Adrenocorticotropic Hormone / metabolism
  • Catalysis
  • Chromatography, Liquid
  • Histidine / metabolism
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Lysine / metabolism*
  • N-Terminal Acetyltransferase A
  • N-Terminal Acetyltransferase E
  • Oligopeptides / metabolism
  • Recombinant Fusion Proteins / analysis
  • Recombinant Fusion Proteins / isolation & purification*
  • Recombinant Fusion Proteins / metabolism*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • His-His-His-His-His-His
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Oligopeptides
  • Recombinant Fusion Proteins
  • Histidine
  • Adrenocorticotropic Hormone
  • Acetyltransferases
  • N-Terminal Acetyltransferase A
  • NAA10 protein, human
  • N-Terminal Acetyltransferase E
  • Lysine