Functional Translatome Proteomics Reveal Converging and Dose-Dependent Regulation by mTORC1 and eIF2α.

ABSTRACT: Regulation of translation is essential during stress. However, the precise sets of proteins regulated by the key translational stress responses-the integrated stress response (ISR) and mTORC1-remain elusive. We developed multiplexed enhanced protein dynamics (mePROD) proteomics, adding signal amplification to dynamic-SILAC and multiplexing, to enable measuring acute changes in protein synthesis. Treating cells with ISR/mTORC1-modulating stressors, we showed extensive translatome modulation with ∼20% of proteins synthesized at highly reduced rates. Comparing translation-deficient sub-proteomes revealed an extensive overlap demonstrating that target specificity is achieved on protein level and not by pathway activation. Titrating cap-dependent translation inhibition confirmed that synthesis

SUBMITTER: Klann K 

PROVIDER: S-EPMC7033560 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature