HAF  : the new player in oxygen-independent HIF-1alpha degradation.
Adaptation to hypoxia is primarily mediated by the hypoxia-inducible transcription factor, HIF. The regulation of HIF activity by the oxygen-dependent degradation of the HIF-1alpha and HIF-2alpha subunits by the pVHL E3 ligase complex has been well characterized. We have recently described the hypoxia-associated factor, HAF, as an E3 ligase for HIF-1alpha that does not degrade HIF-2alpha. Here we summarize the mechanism of HAF-mediated HIF-1alpha degradation and the importance of oxygen-independent HIF-1alpha regulation in cancer. We also discuss the implications of the new HAF: HIF-1alpha degradation pathway with respect to other novel mediators of oxygen-independent HIF-alpha degradation. Finally, we review the significance of HAF as an isoform-specific E3 ligase in light of new information on the non-overlapping functions of HIF-1alpha and HIF-2alpha in cancer.
Koh
Mei Yee
MY
Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX 77030, USA. mykoh@mdanderson.org
Powis
Garth
G
D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000737:chemistry / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011499:Protein Processing, Post-Translational
D002352:Carrier Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010100:Oxygen