Mammalian eIF4E2-GSK3β maintains basal phosphorylation of p53 to resist senescence under hypoxia.

ABSTRACT: Hypoxia modulates senescence, but their physiological link remains unclear. Here, we found that eIF4E2, a hypoxia-activated translation initiation factor, interacted with GSK3β to maintain phosphorylation of p53, thus resisting senescence under hypoxia. RNA-binding protein RBM38 interacted with eIF4E to inhibit the translation of p53, but GSK3β-mediated Ser195 phosphorylation disrupted the RBM38-eIF4E interaction. Through investigation of RBM38 phosphorylation, we found that the eIF4E2-GSK3β pathway specifically regulated proline-directed serine/threonine phosphorylation (S/T-P). Importantly, peptides e2-I or G3-I that blocking eIF4E2-GSK3β interaction can inhibit the basal S/T-P phosphorylation of p53 at multiple sites, therby inducing senescence through transcriptional inhibition. Additi

SUBMITTER: Sun L 

PROVIDER: S-EPMC9107480 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature