EIF3d and eIF3e mediate selective translational control of hypoxia that can be inhibited by novel small molecules.

ABSTRACT: Exposure to hypoxia is linked to increased cellular plasticity and enhanced metastasis; effects which are primarily attributed to the transcriptional activation of large gene programs downstream of hypoxia inducible factors (HIFs). However, translational effects in hypoxia, that likely precede transcriptional effects, have remained largely unexplored. Using ribosome-profiling, we uncovered a selective translational response in acute hypoxia that is eIF3d/eIF3e-dependent and controls downstream hypoxic responses including HIF1a accumulation and cellular invasion. We further demonstrated that eIF3e copy number and an eIF3e-expression signature are associated with worsened outcomes for breast cancer patients. Finally, we identified a class of novel small molecules that target eIF3e specifical

SUBMITTER: Purdy SC 

PROVIDER: S-EPMC12154685 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature