MRNA-to-protein translation in hypoxia

Nancy T. Chee, Ines Lohse, Shaun P. Brothers

Research output: Contribution to journalReview article

7 Scopus citations

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.

Original languageEnglish (US)
Article number49
JournalMolecular Cancer
Volume18
Issue number1
DOIs
StatePublished - Mar 30 2019

Keywords

  • Cancer
  • HIF
  • HIF inhibitors
  • Hypoxia
  • Hypoxia-inducible factor
  • mRNA-to-protein translation

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Cancer Research

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