The EGLN-HIF O2-Sensing System: Multiple Inputs and Feedbacks

被引:210
作者
Ivan, Mircea [1 ,2 ]
Kaelin, William G., Jr. [3 ,4 ,5 ]
机构
[1] Indiana Univ Sch Med, Dept Med, Indianapolis, IN 46202 USA
[2] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA
[3] Howard Hughes Med Inst, Boston, MA 02215 USA
[4] Dana Farber Canc Inst, Boston, MA 02215 USA
[5] Harvard Med Sch, Brigham & Womens Hosp, Boston, MA 02215 USA
关键词
HYPOXIA-INDUCIBLE-FACTOR; TRANSMEMBRANE PROLYL 4-HYDROXYLASE; FACTOR INHIBITING HIF; PROLINE-HYDROXYLATION; METABOLIC SWITCH; CANCER; DOMAIN; ALPHA; ADAPTATION; EXPRESSION;
D O I
10.1016/j.molcel.2017.06.002
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
The EGLN (also called PHD) prolyl hydroxylase enzymes and their canonical targets, the HIF alpha subunits, represent the core of an ancient oxygen-monitoring machinery used by metazoans. In this review, we highlight recent progress in understanding the overlapping versus specific roles of EGLN enzymes and HIF isoforms and discuss how feedback loops based on recently identified noncoding RNAs introduce additional layers of complexity to the hypoxic response. Based on novel interactions identified upstream and downstream of EGLNs, an integrated network connecting oxygen-sensing functions to metabolic and signaling pathways is gradually emerging with broad therapeutic implications.
引用
收藏
页码:772 / 779
页数:8
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