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

摘要: RPS27L (ribosomal protein S27-like) is an evolutionarily conserved ribosomal and a direct p53 target. We recently reported that Rps27l disruption triggers stress to induce p53, causing postnatal death, which can be rescued by Trp53 +/− . Whether how modulates radiosensitivity unknown. Here we report Rps27l −/− ; mice are extremely sensitive radiation due reduced proliferation massive induction of apoptosis in radiation-sensitive organs. Mechanistically, the sensitivity mediated two signaling pathways: (1) activated pathway imbalanced Mdm2/Mdm4 levels E3 ligase activity; (2) DNA damage response MRN/Atm signal as result elevated Mdm2 binding Nbs1 inhibit Nbs1–Atm subsequent Atm activation. Indeed, heterozygous deletion restores signal. Collectively, our study revealed physiological condition under regulates Mdm2/p53 axes maintain confer radioprotection vivo.