C03416: HIF-1aDP, A Constitutively-Expressed form of Hypoxia-Inducible Factor 1a

C03416: HIF-1aDP, A Constitutively-Expressed form of Hypoxia-Inducible Factor 1a
Technical Details:
It has previously been demonstrated that a truncation of HIF-1alpha after amino acid residue 390 results in a constitutively expressed form of the protein. The purpose of this work was to identify mechanisms by which the half-life of the HIF1alpha protein is modulated as a function of cellular O2 concentration, such that the stability of the protein is greater under hypoxic, relative to non-hypoxic conditions. The strategy employed was to introduce mutations into the protein-coding DNA sequence and to identify mutants, which no longer manifested decreased protein stability under non-hypoxic conditions. This strategy was designed to (1) identify important regions of regulation with the HIF-1alpha molecule; and (2) engineer a constitutively stable form of HIF-1alpha that could be utilized for gene therapy of ischemic cardiovascular disease.

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