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Curr Opin Cell Biol. 2001 Apr;13(2):167-71.

HIF-1 and mechanisms of hypoxia sensing.

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Johns Hopkins Hospital, CMSC-1004, 600 North Wolfe Street, Baltimore, Maryland 21287-3914, USA.


Hypoxia-inducible factor 1 (HIF-1) is an oxygen-regulated transcriptional activator that plays essential roles in mammalian development, physiology and disease pathogenesis. The HIF-1 alpha subunit is subjected to oxygen-dependent ubiquitination and proteasomal degradation that is mediated by the von Hippel-Lindau protein. Interaction of HIF-1 alpha transactivation domains with coactivators is induced by hypoxia. The signal transduction pathway remains enigmatic, but involves generation of reactive oxygen species. Nitric oxide induces HIF-1 alpha under non-hypoxic conditions but inhibits hypoxia-induced HIF-1 alpha expression.

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