What is the hypoxia inducible factor pathway?
Hypoxia inducible factor (HIF) senses and coordinates cellular responses to hypoxia. HIF is a heterodimer consisting of one of three alpha (α) subunits and a beta (β) subunit. HIF-β is constitutively expressed, whereas HIF-α is induced by hypoxia.
What is the function of hypoxia inducible factor?
Hypoxia-Inducible Factor (HIF)-1 is a dimeric protein complex that plays an integral role in the body’s response to low oxygen concentrations, or hypoxia. HIF-1 is among the primary genes involved in the homeostatic process, which can increase vascularization in hypoxic areas such as localized ischemia and tumors.
What genes are regulated by HIF?
The target genes regulated by HIF-1α are mainly EPO, VEGF, HO-1, ADM, and Glut-1. EPO is the first identified gene related to hypoxia which in turn led to the discovery of HIF (Semenza and Wang, 1992).
How does HIF regulate transcription?
Upon hypoxia, the HIF alpha subunits are stabilized and accumulate in the nucleus, where they dimerize with HIF1B, allowing them to bind to DNA and stimulate the transcription of their target genes.
What is HIF pathway?
Hypoxia-inducible factor (HIF) is an alpha,beta-heterodimeric transcription factor that mediates cellular responses to low oxygen concentration via the transcriptional activation of specific genes involved in both tumorogenesis and angiogenesis.
How is HIF-1 activated?
HIF-1α protein synthesis can be induced by many different growth factors and cytokines, such as insulin,54 insulin-like growth factors55 or PDGF. P42/44 mitogen-activated kinase (MAPK) has been implicated in phosphorylation of HIF-1α and activation of MAPK amplifies transcriptional response of HIF.
Is HIF a transcription factor?
HIF is a transcriptional factor that plays a role in the physiologic responses to hypoxia. HIF-1 is a heterodimer consisting of an oxygen-regulated HIF-1α and HIF-2α subunits and a constitutively expressed HIF-1β subunit.
What does HIF bind to?
HIF-α binds chromatin in stoichiometric ratio with HIF-1β Classically, HIF binds to chromatin as a canonical heterodimer of α- and β-subunits 24, 33. However, several reports have described non-canonical associations of HIF-α subunits with other transcription factors 27-29.
What does HIF mean?
Hypoxia-inducible factor (HIF) is a sensor of hypoxia and a regulator of the cellular hypoxic response. HIF is a heterodimeric complex comprised of an α-subunit, usually HIF-1α, and a β-subunit, usually the aryl hydrocarbon receptor nuclear translocator (ARNT).
How does HIF-1 alpha work?
Under hypoxic conditions, Hif-1 alpha translocates to the cell nucleus and associates with Hif-1 beta. This complex then binds to the HRE region of the DNA resulting in the transcription of genes that are involved in a multitude of processes including erythropoesis, glycolysis, and angiogenesis.