Hypoxia-Inducible Factor-1 (HIF-1)
| Autor: | Max Costa, Qingdong Ke |
|---|---|
| Rok vydání: | 2006 |
| Předmět: | |
| Zdroj: | Molecular Pharmacology. 70:1469-1480 |
| ISSN: | 1521-0111 0026-895X |
| DOI: | 10.1124/mol.106.027029 |
| Popis: | 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-1beta and an oxygen-regulated subunit HIF-1alpha (or its paralogs HIF-2alpha and HIF-3alpha). The stability and activity of the alpha 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-1alpha trigger its association with pVHL E3 ligase complex, leading to HIF-1alpha degradation via ubiquitin-proteasome pathway. In hypoxia, the HIF-1alpha 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|