Scientific background: |
HIF-1alpha (Hypoxia-inducible factor 1alpha,HIF1A) is a transcription factor that mediates cellular and systemic homeostatic responses to reduced O2 availability in mammals, including angiogenesis, erythropoiesis and glycolysis. This gene was mapped to 14q21-q24. HIF-1alpha transactivate genes required for energy metabolism and tissue perfusion and is necessary for embryonic development and tumor explant growth. HIF-1alpha is over expressed during carcinogenesis, myocardial infarction and wound healing. It is crucial for the cellular response to hypoxia and is frequently over expressed in human cancers, resulting in the activation of genes essential for cell survival. HIF-1alpha regulates the survival and function in the inflammatory microenvironment directly. It is a transcription factor that plays a pivotal role in cellular adaptation to changes in oxygen availability. |
References: |
1. Sutter, C. H.; Laughner, E.; Semenza, G. L. : Hypoxia-inducible factor 1-alpha protein expression is controlled by oxygen-regulated ubiquitination that is disrupted by deletions and missense mutations. Proc. Nat. Acad. Sci. 97: 4748-4753, 2000.
2. Elson, D. A.; Thurston, G.; Huang, L. E.; Ginzinger, D. G.; McDonald, D. M.; Johnson, R. S.; Arbeit, J. M. : Induction of hypervascularity without leakage or inflammation in transgenic mice overexpressing hypoxia-inducible factor-1-alpha. Genes Dev. 15: 2520-2532, 2001.
3. Koshiji, M.; To, K. K.-W.; Hammer, S.; Kumamoto, K.; Harris, A. L.; Modrich, P.; Huang, L. E. : HIF-1-alpha induces genetic instability by transcriptionally downregulating MutS-alpha expression. Molec. Cell 17: 793-803, 2005.
4. Ivan, M.; Kondo, K.; Yang, H.; Kim, W.; Valiando, J.; Ohh, M.; Salic, A.; Asara, J. M.; Lane, W. S.; Kaelin, W. G., Jr. : HIF-alpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O(2) sensing. Science 292: 464-468, 2001. |