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

Genes and Development - Tập 15 Số 20 - Trang 2675-2686 - 2001
Patrick C. Mahon1, Kiichi Hirota2, Gregg L. Semenza1
1Institute of Genetic Medicine, Departments of Pediatrics and Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-3914, USA.
2Johns Hopkins University

Tóm tắt

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 O2regulated 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 O2concentration.

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Genes and Development

Tập 15 Số 20

2675-2686

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