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Hypoxia-inducible factor-1 (HIF-1),composed of HIF-α andHIF-β subunits,is a heterodimeric transcriptional activator.In response to hypoxia,stimulation of growth factors,andactivation of oncogenes as well as carcinogens,HIF-1α isoverexpressed and/or activated and targets those geneswhich are required for angiogenesis,metabolic adaptationto Iow oxygen and promotes survival.HIF-1 is critical forboth physiological and pathological processes.Several dozensof putative direct HIF-1 target genes have been identifiedon the basis of one or more cis-acting hypoxia-responseelements that contain an HIF-1 binding site.A variety ofregulators including growth factors,genetic alterations,stressactivators,and some carcinogens have been documentedfor regulation of HIF-1 in which several signaling pathwaysare involved depending on the stimuli and cell types.Activation of HIF-1 in combination with activated signalingpathways and regulators is implicated in tumour progressionand prognosis.This review presents a summary of thestructure and function of HIF-1α,and correlation amongspecific regulators and their signaling pathways.
Hypoxia-inducible factor-1 (HIF-1), composed of HIF-α and HIF-β subunits, is a heterodimeric transcriptional activator. In response to hypoxia, stimulation of growth factors, and activation of oncogenes as well as carcinogens, HIF-1α isoverexpressed and / or activated and targets those geneswhich are required for angiogenesis, metabolic adaptationto Iow oxygen and promotes survival. HIF-1 is critical forboth physiological and pathological processes. Federation dozens of putative direct HIF-1 target genes have been identified on the basis of one or more cis-acting hypoxia-responseelements that contain an HIF-1 binding site. A variety ofregulators including growth factors, genetic alterations, stress activators, and some carcinogens have been documentedfor regulation of HIF-1 in which several signaling pathwaysare involved depending on the stimuli and cell types. Activation of HIF-1 in combination with activated signalingpathways and regulators is implicated in tumor progression and prognosis.This review pre sents a summary of the structure and function of HIF-1α, and correlation amongspecific regulators and their signaling pathways.