MINIREVIEW Hypoxia-Inducible Factor-1 (HIF-1)

Adaptation to low oxygen tension (hypoxia) in cells and tissues leads to the transcriptional induction of a series of genes that participate in angiogenesis, iron metabolism, glucose metabo-lism, and cell proliferation/survival. The primary factor mediat-ing this response is the hypoxia-inducible factor-1 (HIF-1), an oxygen-sensitive transcriptional activator. HIF-1 consists of a constitutively expressed subunit HIF-1 and an oxygen-regu-lated subunit HIF-1 (or its paralogs HIF-2 and HIF-3). The stability and activity of the subunit of HIF are regulated by its post-translational modifications such as hydroxylation, ubiq-uitination, acetylation, and phosphorylation. In normoxia, hy-droxylation of two proline residues and acetylation of a lysine residue at the oxygen-dependent degradation domain (ODDD) of HIF-1 trigger its association with pVHL E3 ligase complex