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Biochem Biophys Res Commun. 2001 Oct 5;287(4):808-13.

Expression and characterization of hypoxia-inducible factor (HIF)-3alpha in human kidney: suppression of HIF-mediated gene expression by HIF-3alpha.

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1
Department of Public Health and Molecular Toxicology, School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. haras@pharm.kitasato-u.ac.jp

Abstract

Hypoxia inducible factors (HIFs) are heterodimeric transcription factors that regulate a number of adaptive responses to low oxygen tension. They are composed of alpha- and beta-subunits that belong to the basic helix-loop-helix-PAS superfamily. Here we examined the expression of HIF-alpha subunit proteins in the human kidney and found that, in addition to HIF-1alpha and -2alpha, HIF-3alpha was also expressed. The sequence analysis revealed that, like mouse HIF-3alpha, human HIF-3alpha has high similarity with HIF-1alpha and -2alpha in the bHLH and PAS domains, but lacks structures for transactivation found in the C-terminus of HIF-1alpha and -2alpha. Furthermore, we performed reporter gene analysis and showed that HIF-3alpha suppresses hypoxia-inducible HIF-mediated gene expression. HIF-3alpha might be a negative regulator of hypoxia-inducible gene expression in the human kidney.

PMID:
11573933
DOI:
10.1006/bbrc.2001.5659
[Indexed for MEDLINE]

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