| First Author | Zhao Y | Year | 2018 |
| Journal | Cell Death Dis | Volume | 9 |
| Issue | 2 | Pages | 145 |
| PubMed ID | 29396424 | Mgi Jnum | J:301795 |
| Mgi Id | MGI:6506926 | Doi | 10.1038/s41419-017-0192-3 |
| Citation | Zhao Y, et al. (2018) Inactivation of ribosomal protein S27-like confers radiosensitivity via the Mdm2-p53 and Mdm2-MRN-ATM axes. Cell Death Dis 9(2):145 |
| abstractText | 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 binding of Nbs1 to inhibit Nbs1-Atm binding and subsequent Atm activation. Indeed, heterozygous deletion of Mdm2 restores the MRN/Atm signal. Collectively, our study revealed a physiological condition under which Rps27l regulates the Mdm2/p53 and MRN/Atm axes to maintain DNA damage response and to confer radioprotection in vivo. |
