mRNA-to-protein translation in hypoxia.

Abstract:

:Cells respond to hypoxia by shifting cellular processes from general housekeeping functions to activating specialized hypoxia-response pathways. Oxygen plays an important role in generating ATP to maintain a productive rate of protein synthesis in normoxia. In hypoxia, the rate of the canonical protein synthesis pathway is significantly slowed and impaired due to limited ATP availability, necessitating an alternative mechanism to mediate protein synthesis and facilitate adaptation. Hypoxia adaptation is largely mediated by hypoxia-inducible factors (HIFs). While HIFs are well known for their transcriptional functions, they also play imperative roles in translation to mediate hypoxic protein synthesis. Such adaptations to hypoxia are often hyperactive in solid tumors, contributing to the expression of cancer hallmarks, including treatment resistance. The current literature on protein synthesis in hypoxia is reviewed here, inclusive of hypoxia-specific mRNA selection to translation termination. Current HIF targeting therapies are also discussed as are the opportunities involved with targeting hypoxia specific protein synthesis pathways.

journal_name

Mol Cancer

journal_title

Molecular cancer

authors

Chee NT,Lohse I,Brothers SP

doi

10.1186/s12943-019-0968-4

subject

Has Abstract

pub_date

2019-03-30 00:00:00

pages

49

issue

1

issn

1476-4598

pii

10.1186/s12943-019-0968-4

journal_volume

18

pub_type

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