Oxygen sensing by metazoans: The central role of the HIF hydroxylase pathway

被引：2512

作者：

Kaelin, William G., Jr. ^{[1
,2
,3
]}

Ratcliffe, Peter J. ^{[4
]}

机构：

[1] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA

[3] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA

[4] Univ Oxford, Oxford OX3 7BN, England

来源：

MOLECULAR CELL | 2008年 / 30卷 / 04期

关键词：

D O I：

10.1016/j.molcel.2008.04.009

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

HIF plays a central role in the transcriptional response to changes in oxygen availability. The PHD family of oxygen-dependent prolyl hydroxylases plays a pivotal role in regulating HIF stability. The biochemical properties of these enzymes make them well suited to act as oxygen sensors. They also respond to other intracellular signals, including reactive oxygen species, nitric oxide, and certain metabolites, that can modulate the hypoxic response. HIF transcriptional activity is further tuned by FIH1-mediated asparagine hydroxylation. HIF affects signaling pathways that influence development, metabolism, inflammation, and integrative physiology. Accordingly, HIF-modulatory drugs are now being developed for diverse diseases.

引用

页码：393 / 402

页数：10

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