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-1α subunit is subjected to oxygen-dependent ubiquitination and proteasomal degradation that is mediated by the von Hippel-Lindau protein. Interaction of HIF-1α 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-1α under non-hypoxic conditions but inhibits hypoxia-induced HIF-1α expression.