PT  - JOURNAL ARTICLE
AU  - Qingdong Ke
AU  - Max Costa
TI  - Hypoxia-Inducible Factor-1 (HIF-1)
AID  - 10.1124/mol.106.027029
DP  - 2006 Nov 01
TA  - Molecular Pharmacology
PG  - 1469--1480
VI  - 70
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/70/5/1469.short
4100  - http://molpharm.aspetjournals.org/content/70/5/1469.full
SO  - Mol Pharmacol2006 Nov 01; 70
AB  - 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 metabolism, and cell proliferation/survival. The primary factor mediating this response is the hypoxia-inducible factor-1 (HIF-1), an oxygen-sensitive transcriptional activator. HIF-1 consists of a constitutively expressed subunit HIF-1β and an oxygen-regulated subunit HIF-1α (or its paralogs HIF-2α and HIF-3α). The stability and activity of the α subunit of HIF are regulated by its post-translational modifications such as hydroxylation, ubiquitination, acetylation, and phosphorylation. In normoxia, hydroxylation of two proline residues and acetylation of a lysine residue at the oxygen-dependent degradation domain (ODDD) of HIF-1α trigger its association with pVHL E3 ligase complex, leading to HIF-1α degradation via ubiquitin-proteasome pathway. In hypoxia, the HIF-1α subunit becomes stable and interacts with coactivators such as cAMP response element-binding protein binding protein/p300 and regulates the expression of target genes. Overexpression of HIF-1 has been found in various cancers, and targeting HIF-1 could represent a novel approach to cancer therapy. The American Society for Pharmacology and Experimental Therapeutics