HIF 1 is stabilized under circumstances because of a reduction in PHD action and interacts with HIF 1. the resulting HIF 1 binds to its cognate transcriptional enhancer sequence, the responsive component, and induces the expression of various genes associated with the variation of cellular kcalorie burning to hypoxia, escaping from hypoxia, and reduces hypoxia, and so forth. As well as the PHDs VHL mediated mechanism, other mechanisms have now been reported Oprozomib 935888-69-0 to work in the regulation of HIF 1 activity. As an example, balance of HIF 1 can be regulated in a receptor of activated protein kinase C dependent fashion. Interaction with RACK1 results in the oxygen independent degradation of HIF 1 because RACK1 competitively inhibits the interaction of HIF 1 to heat-shock protein 90 which stabilizes the HIF 1 protein. Also, it was lately elucidated that HIF 1 protein synthesis is determined by a phosphatidylinositol 3 kinase Akt mammalian target of the rapamycin signaling transduction pathway because of the existence of Gene expression a polypyrimidine tract in the 5thth untranslated region of HIF 1 mRNA. More over, the posttranslational modification of HIF 1 also plays a critical role in stimulating the transactivational activity of HIF 1. Under normoxic conditions, component inhibiting HIF 1 becomes active and hydroxylates an asparagine residue of HIF 1. the hydroxylation blocks the employment of co factors p300 and CBP, resulting in the reduction of HIF 1,s transactivational activity. Phosphorylation of HIF 1 by mitogen activated protein kinase and ERK signaling pathways can be known to play a significant role in the up-regulation of its transactivation activity. An appealing model for the role of HIF 1 in tumor radioresistance was suggested HDAC6 inhibitor recently, radiation initiates HIF 1 in a great tumor consequently of both the upsurge in oxidative stress and improvement in glucose and oxygen availabilities, HIF 1 induces the expression of VEGF, VEGF protects endothelial cells from the cytotoxic effects of radiation, and the radioprotected tumor blood vessels guarantee the supply of oxygen and nutrients to tumor cells and promote tumor growth. the feasibility of the type has been confirmed by these information. Visual imaging having an HIF 1 dependent reporter gene revealed that intratumor HIF 1 activity is dramatically induced by radiation therapy. A hypoxia conditioned medium, which contained a top degree of VEGF, notably paid down the incidence of radiation-induced apoptosis of human umbilical vein endothelial cells. An HIF 1 chemical, YC 1, or a neutralizing antibody against VEGF significantly induced apoptosis of endothelial cells and decreased microvessel density ather radiation therapy, causing a radiosensitizing influence in a tumor growth delay analysis.