| First Author | Kon N | Year | 2021 |
| Journal | Genes Dev | Volume | 35 |
| Issue | 1-2 | Pages | 59-64 |
| PubMed ID | 33303641 | Mgi Jnum | J:314680 |
| Mgi Id | MGI:6823317 | Doi | 10.1101/gad.340919.120 |
| Citation | Kon N, et al. (2021) mTOR inhibition acts as an unexpected checkpoint in p53-mediated tumor suppression. Genes Dev 35(1-2):59-64 |
| abstractText | Here, we showed that the acetylation-defective p53-4KR mice, lacking the ability of cell cycle arrest, senescence, apoptosis, and ferroptosis, were tumor prone but failed to develop early-onset tumors. By identifying a novel p53 acetylation site at lysine K136, we found that simultaneous mutations at all five acetylation sites (p53-5KR) diminished its remaining tumor suppression function. Moreover, the embryonic lethality caused by the deficiency of mdm2 was fully rescued in the background of p53(5KR/5KR) , but not p53(4KR/4KR) background. p53-4KR retained the ability to suppress mTOR function but this activity was abolished in p53-5KR cells. Notably, the early-onset tumor formation observed in p53(5KR/5KR) and p53-null mice was suppressed upon the treatment of the mTOR inhibitor. These results suggest that p53-mediated mTOR regulation plays an important role in both embryonic development and tumor suppression, independent of cell cycle arrest, senescence, apoptosis, and ferroptosis. |
