Hypoxia-inducible factor-1 (HIF-1), composed of HIF-α andHIF-13 subunits, is a heteroclimeric transcriptional activator.In response to hypoxia, stimulation of growth factors, andactivation of oncogenes as well as car...Hypoxia-inducible factor-1 (HIF-1), composed of HIF-α andHIF-13 subunits, is a heteroclimeric transcriptional activator.In response to hypoxia, stimulation of growth factors, andactivation of oncogenes as well as carcinogens, HIF-1α is overexpressed and/or activated and targets those geneswhich are required for angiogenesis, metabolic adaptationto low 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 c/s-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.展开更多
基金Supported by Key Project of Science and Technology from Committee of Beijing Science and Technology (H020920030390)
文摘Hypoxia-inducible factor-1 (HIF-1), composed of HIF-α andHIF-13 subunits, is a heteroclimeric transcriptional activator.In response to hypoxia, stimulation of growth factors, andactivation of oncogenes as well as carcinogens, HIF-1α is overexpressed and/or activated and targets those geneswhich are required for angiogenesis, metabolic adaptationto low 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 c/s-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.
