Inactivation of ribosomal protein S27-like confers radiosensitivity via the Mdm2-p53 and Mdm2-MRN-ATM axes.

ABSTRACT: RPS27L (ribosomal protein S27-like) is an evolutionarily conserved ribosomal protein and a direct p53 target. We recently reported that Rps27l disruption triggers ribosomal stress to induce p53, causing postnatal death, which can be rescued by Trp53 ^+/- . Whether and how Rps27l modulates radiosensitivity is unknown. Here we report that Rps27l ^-/- ; Trp53 ^+/- mice are extremely sensitive to radiation due to reduced proliferation and massive induction of apoptosis in radiation-sensitive organs. Mechanistically, the radiation sensitivity is mediated by two signaling pathways: (1) activated p53 pathway due to imbalanced Mdm2/Mdm4 levels and reduced E3 ligase activity; and (2) reduced DNA damage response due to reduced MRN/Atm signal as a result of elevated Mdm2

SUBMITTER: Zhao Y 

PROVIDER: S-EPMC5833388 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature