[PDF][PDF] The EGLN-HIF O2-sensing system: multiple inputs and feedbacks

M Ivan, WG Kaelin - Molecular cell, 2017 - cell.com
M Ivan, WG Kaelin
Molecular cell, 2017cell.com
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 …
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.
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