FIH-1: A novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity

P. C. Mahon, K. Hirota, G. L. Semenza

Research output: Contribution to journalArticlepeer-review

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a master regulator of oxygen homeostasis that controls angiogenesis, erythropoiesis, and glycolysis via transcriptional activation of target genes under hypoxic conditions. O2-dependent binding of the von Hippel-Lindau (VHL) tumor suppressor protein targets the HIF-1α subunit for ubiquitination and proteasomal degradation. The activity of the HIF-1α transactivation domains is also O2 regulated by a previously undefined mechanism. Here, we report the identification of factor inhibiting HIF-1 (FIH-1), a protein that binds to HIF-1α and inhibits its transactivation function. In addition, we demonstrate that FIH-1 binds to VHL and that VHL also functions as a transcriptional corepressor that inhibits HIF-1α transactivation function by recruiting histone deacetylases. Involvement of VHL in association with FIH-1 provides a unifying mechanism for the modulation of HIF-1α protein stabilization and transcriptional activation in response to changes in cellular O2 concentration.

Original languageEnglish (US)
Pages (from-to)2675-2686
Number of pages12
JournalGenes and Development
Volume15
Issue number20
DOIs
StatePublished - Oct 15 2001

Keywords

  • Corepressor
  • Histone deacetylase
  • Hypoxia
  • Transactivation

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

Fingerprint

Dive into the research topics of 'FIH-1: A novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity'. Together they form a unique fingerprint.

Cite this