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

Hypoxia inducible factors (HIFs) are heterodimeric transcription factors th at 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-h elix-PAS superfamily. Here we examined the expression of HIF-alpha subunit proteins in the human kidney and found that, in addition to HIF-1 alpha and -2 alpha, HIF-3 alpha was also expressed. The sequence analysis revealed t hat, like mouse HIF-3 alpha, human HIF-3 alpha has high similarity with HIF -1 alpha and -2 alpha in the bHLH and PAS domains, but lacks structures for transactivation found in the C-terminus of HIF-1 alpha and -2 alpha. Furth ermore, we performed reporter gene analysis and showed that HIF-3 alpha sup presses hypoxia-inducible HIF-mediated gene expression. HIF-3 alpha might b e a negative regulator of hypoxia-inducible gene expression in the human ki dney. (C) 2001 Academic Press.