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ACTIVATION OF HYPOXIA-INDUCIBLE FACTOR 1a BY OXYGEN INDEPENDENT PATHWAYSThe increasing body of evidence supports that hypoxia-inducible factor 1a (HIF-1a), a dominant subunit of HIF1 heterodimer, is not solely induced by the effect of hypoxia. Apart from CoCl2 and iron chelators that serve as the putative HIF-1a activators, genetic alterations and other epigenetic effects are able to induce HIF-1a protein accumulation and to activate HIF-1 functions. Activation of oncogenes (H-ras and v-src) involving signaling cascades (PI3K and MAPK) and loss-of-function mutations in tumor suppressor genes (VHL, PTEN, and p53) result in HIF-1a protein accumulation and increased expression of downstream target genes. HIF-1a can also be induced by a number of agonists. Activation of HIF-1a is often an interactive consequence of multiple factors. No Comments » Add comments |
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