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Hypoxia-inducible factor 1: oxygen homeostasis and disease pathophysiology
1Institute 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
Abstract:
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.