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Mol Cell. 2017 Jun 15;66(6):772-779. doi: 10.1016/j.molcel.2017.06.002.

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

Author information

1
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. Electronic address: mivan@iu.edu.
2
Howard Hughes Medical Institute, Boston, MA 02215, USA; Dana-Farber Cancer Institute, Boston, MA 02215, USA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.

Abstract

The EGLN (also called PHD) prolyl hydroxylase enzymes and their canonical targets, the HIFα 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.

KEYWORDS:

EGLN; HIF1α; HIF2α; PHD; hypoxia; lncRNA; metabolism; miRNA; noncoding RNA; oxygen

PMID:
28622522
PMCID:
PMC5613951
DOI:
10.1016/j.molcel.2017.06.002
[Indexed for MEDLINE]
Free PMC Article

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