Hypoxia-inducible factor 1 (HIF-1) activates transcription of genes encodin
g proteins that mediate adaptive responses to reduced oxygen availability.
The HIF-1 beta subunit is constitutively expressed, whereas the HIF-1 alpha
subunit is subject to ubiquitination and proteasomal degradation, a proces
s 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 t
herapeutic approach to these common causes of mortality.