Effect of protein kinase and phosphatase inhibitors on expression of hypoxia inducible factor 1

Guang L. Wang, Bing Hua Jiang, Gregg L. Semenza

Research output: Contribution to journalArticle

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric bHLH-PAS protein essential for erythropoietin gene transcription in hypoxic cells. Here we show that both 2-aminopurine and sodium fluoride, inhibitors of serine/threonine kinases and phosphatases, respectively, interfered with the hypoxic induction of HIF-1 DNA-binding activity and expression of HIF-1α and HIF-1β(ARNT) subunits. Genistein, an inhibitor of tyrosine kinases, completely blocked the synthesis of both HIF-1 subunits as well as HIF-1 DNA-binding activity. Sodium orthovanadate, an inhibitor of tyrosine phosphatases increased the basal level of HIF-1 proteins and HIF-1 activity. These data suggest that protein phosphorylation events play an important role in the hypoxia signal-transduction pathway that leads to synthesis of HIF-1α and HIF-1β proteins and the induction of HIF-1 DNA-binding activity.

Original languageEnglish (US)
Pages (from-to)669-675
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume216
Issue number2
DOIs
StatePublished - Jan 1 1995

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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