Functions as a master transcriptional regulator of theadaptive response to hypoxia. Under hypoxic conditions, activatesthe transcription of over 40 genes, including erythropoietin,glucose transporters, glycolytic enzymes, vascular endothelialgrowth factor, HILPDA, and other genes whose protein productsincrease oxygen delivery or facilitate metabolic adaptation tohypoxia. Plays an essential role in embryonic vascularization,tumor angiogenesis and pathophysiology of ischemic disease. Bindsto core DNA sequence 5'-[AG]CGTG-3' within the hypoxia responseelement (HRE) of target gene promoters. Activation requiresrecruitment of transcriptional coactivators such as CREBPB andEP300. Activity is enhanced by interaction with both, NCOA1 orNCOA2. Interaction with redox regulatory protein APEX seems toactivate CTAD and potentiates activation by NCOA1 and CREBBP.Involved in the axonal distribution and transport of mitochondriain neurons during hypoxia.
Tissue Specificity
Expressed in most tissues with highest levelsin kidney and heart. Overexpressed in the majority of common humancancers and their metastases, due to the presence of intratumoralhypoxia and as a result of mutations in genes encodingoncoproteins and tumor suppressors. A higher level expression seenin pituitary tumors as compared to the pituitary gland.
HIF-1 (Hypoxia-inducible factor 1, 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-1 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-1 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.
[list_product_images]Western blot analysis of hydroxylated HIF-1 alpha expression in nuclear extracts of A549 cells treated with MG132. Hydroxyproline is not recognized on HIF-1alpha when cells are first treated with DFO, a prolyl hydroxylase inhibitor that prevents HIF hydroxylation (left panel). HIF-1 alpha at 110KD was detected using rabbit anti-HIF-1alpha hydroxyP564 polyclonal antibody (Catalog # A00013) at 1:1000. Control staining is shown using conventional anti-HIF-1 alpha (right panel). Personal Communication, L. Neckers and O. Aprelikova, NCI, Bethesda, MD.[/list_product_images]