• DOI:10.1124/mol.106.027029
• Corpus ID: 2522614

Hypoxia-Inducible Factor-1 (HIF-1)

@article{Ke2006HypoxiaInducibleF,
  title={Hypoxia-Inducible Factor-1 (HIF-1)},
  author={Qingdong Ke and Max Costa},
  journal={Molecular Pharmacology},
  year={2006},
  volume={70},
  pages={1469 - 1480}
}

• Qingdong Ke, Max Costa
• Published 1 November 2006
• Biology
• Molecular Pharmacology

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.