The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity.

The FIH hydroxylase is a cellular peroxide sensor that modulates HIF transcriptional activity.
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DOI:
10.1038/embor.2012.9
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发表时间:
2012-03-01
期刊:
影响因子:
7.7
通讯作者:
Ratcliffe, Peter J.
Ratcliffe, Peter J.
中科院分区:
生物学2区
文献类型:
--
作者:
Masson, Norma;Singleton, Rachelle S.;Sekirnik, Rok;Trudgian, David C.;Ambrose, Lucy J.;Miranda, Melroy X.;Tian, Ya-Min;Kessler, Benedikt M.;Schofield, Christopher J.;Ratcliffe, Peter J.

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缺氧和氧化应激可以共存于生物系统中,氧化应激被认为是通过“氧敏感”缺氧诱导因子(HIF)脯氨酰和天冬酰胺酰羟化酶的失活来激活缺氧途径。在这里,我们表明,尽管降低敏感性细胞缺氧,HIF天冬酰胺酰羟化酶-被称为FIH,因子抑制HIF-是惊人的更敏感的过氧化物比HIF脯氨酰羟化酶。这些对比的敏感性表明,氧化应激是不太可能的信号缺氧直接的HIF系统,但缺氧和氧化应激可以相互作用的HIF转录输出的不同调节功能。
Hypoxic and oxidant stresses can coexist in biological systems, and oxidant stress has been proposed to activate hypoxia pathways through the inactivation of the ‘oxygen-sensing’ hypoxia-inducible factor (HIF) prolyl and asparaginyl hydroxylases. Here, we show that despite reduced sensitivity to cellular hypoxia, the HIF asparaginyl hydroxylase—known as FIH, factor inhibiting HIF—is strikingly more sensitive to peroxide than the HIF prolyl hydroxylases. These contrasting sensitivities indicate that oxidant stress is unlikely to signal hypoxia directly to the HIF system, but that hypoxia and oxidant stress can interact functionally as distinct regulators of HIF transcriptional output.
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