Critical hypoxia-inducible factor-1alpha residues, products and methods related thereto

摘要

A modified HIF-1alpha protein is capable of avoiding degradation by failing to bind or failing to bind properly to pVHL. This modified HIF-1alpha protein can be used in research regarding hypoxic response as well as in treatments for hypoxic-related conditions. The amino acids at residues 568, 570, 571, and 573 of HIF-1alpha play a critical role in mediating degradation at normoxia. Further, the pairs of residues at 560 and 561, and at 566 and 567 are critical as well. Resistance to pVHL-mediated degradation can be imparted using specific alterations at these residues. Active fragments of the HIF-1alpha N-TAD may also be used as treatments for hypoxic-related conditions.