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.
Copyright © 2017. Published by Elsevier Inc.
MeSH terms
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Adaptation, Physiological
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Animals
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Antineoplastic Agents / therapeutic use
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Basic Helix-Loop-Helix Transcription Factors / antagonists & inhibitors
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Basic Helix-Loop-Helix Transcription Factors / metabolism*
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Endoglin / metabolism*
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Feedback, Physiological
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
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Neoplasms / drug therapy
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Neoplasms / enzymology*
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Neoplasms / genetics
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Neoplasms / pathology
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Oxygen / metabolism*
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RNA, Untranslated / genetics
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RNA, Untranslated / metabolism
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Signal Transduction* / drug effects
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Tumor Hypoxia
Substances
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Antineoplastic Agents
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Basic Helix-Loop-Helix Transcription Factors
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Endoglin
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Hypoxia-Inducible Factor 1, alpha Subunit
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RNA, Untranslated
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endothelial PAS domain-containing protein 1
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Oxygen