Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology.
Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encoding proteins that mediate adaptive responses to reduced oxygen availability. The HIF-1beta subunit is constitutively expressed, whereas the HIF-1alpha subunit is subject to ubiquitination and proteasomal degradation, a process that is inhibited under hypoxic conditions. Recent data indicate that HIF-1 plays major roles in the prevention of myocardial and cerebral ischemia and in the pathogenesis of pulmonary hypertension and cancer. Modulation of HIF-1 activity by genetic or pharmacological means could provide a novel therapeutic approach to these common causes of mortality.
Semenza
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Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Johns Hopkins Hospital, CMSC-1004, 600 North Wolfe Street, Baltimore, MD 21287-3914, USA. gsemenza@jhmi.edu
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism / Q000517:prevention & control; D002318:Cardiovascular Diseases / Q000503:physiopathology* / Q000517:prevention & control; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D006706:Homeostasis; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019194:Ischemic Preconditioning; D009369:Neoplasms / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors
D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors; D010100:Oxygen