Translating the Hypoxic Response—the Role of HIF Protein Translation in the Cellular Response to Low Oxygen

Abstract

Hypoxia-Inducible Factors (HIFs) play essential roles in the physiological response to low oxygen in all multicellular organisms, while their deregulation is associated with human diseases. HIF levels and activity are primarily controlled by the availability of the oxygen-sensitive HIFα subunits, which is mediated by rapid alterations to the rates of HIFα protein production and degradation. While the pathways that control HIFα degradation are understood in great detail, much less is known about the targeted control of HIFα protein synthesis and what role this has in controlling HIF activity during the hypoxic response. This review will focus on the signalling pathways and RNA binding proteins that modulate HIFα mRNA half-life and/or translation rate, and their contribution to hypoxia-associated diseases.