Redefining the role of eIF4E dose in development, cancer, and protein synthesis

ABSTRACT: eIF4E, the major cap-binding protein, has long been considered limiting for translating the mammalian genome. However, the requirement for eIF4E dose at an organismal level remains unexplored. By generating an Eif4e haploinsufficient mouse, we surprisingly found that 50% reduction in eIF4E, while compatible with normal development and global protein synthesis, significantly impeded cellular transformation and tumorigenesis. Genome-wide translational profiling uncovered a translational program induced by oncogenic transformation and revealed a critical role for eIF4E dose specifically in translating a network of mRNAs enriched for a unique 5’UTR signature. In particular, we demonstrate that eIF4E dose is essential for translating mRNAs regulating reactive oxygen species (ROS) that fuel tran

ORGANISM(S): Mus musculus

SUBMITTER: Davide Ruggero 

PROVIDER: E-GEOD-68238 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress