HAF The new player in oxygen-independent HIF-1α degradation

被引:29
作者
Koh, Mei Yee [1 ]
Powis, Garth [1 ]
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA
关键词
HAF; SART-1; HIF-1; alpha; HIF-2; hypoxia; cancer; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ACUTE MYELOID-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; FACTOR 1-ALPHA HIF-1-ALPHA; COLONY-STIMULATING FACTOR; HIPPEL-LINDAU PROTEIN; CANCER STEM-CELLS; HIF-ALPHA; GEMTUZUMAB OZOGAMICIN; HIF-2-ALPHA PROMOTES;
D O I
10.4161/cc.8.9.8303
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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-1 alpha and HIF-2 alpha 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-1 alpha that does not degrade HIF-2 alpha. Here we summarize the mechanism of HAF-mediated HIF-1 alpha degradation and the importance of oxygen-independent HIF-1 alpha regulation in cancer. We also discuss the implications of the new HAF: HIF-1 alpha degradation pathway with respect to other novel mediators of oxygen-independent HIF- a 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-1 alpha and HIF-2 alpha in cancer.
引用
收藏
页码:1359 / 1366
页数:8
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