化学
缺氧诱导因子
羟基化
缺氧(环境)
缺氧诱导因子1
下调和上调
加氧酶
基因亚型
酶
细胞生物学
转录因子
氧气
生物化学
基因
生物
有机化学
作者
Yue Wu,Zhihong Li,M.A. McDonough,Christopher J. Schofield,Xiaojin Zhang
标识
DOI:10.1021/acs.jmedchem.1c00415
摘要
Factor inhibiting hypoxia-inducible factor (FIH) is a JmjC domain 2-oxogluarate and Fe(II)-dependent oxygenase that catalyzes hydroxylation of specific asparagines in the C-terminal transcriptional activation domain of hypoxia-inducible factor alpha (HIF-α) isoforms. This modification suppresses the transcriptional activity of HIF by reducing its interaction with the transcriptional coactivators p300/CBP. By contrast with inhibition of the HIF prolyl hydroxylases (PHDs), inhibitors of FIH, which accepts multiple non-HIF substrates, are less studied; they are of interest due to their potential ability to alter metabolism (either in a HIF-dependent and/or -independent manner) and, provided HIF is upregulated, to modulate the course of the HIF-mediated hypoxic response. Here we review studies on the mechanism and inhibition of FIH. We discuss proposed biological roles of FIH including its regulation of HIF activity and potential roles of FIH-catalyzed oxidation of non-HIF substrates. We highlight potential therapeutic applications of FIH inhibitors.
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