| First Author | Johmura Y | Year | 2016 |
| Journal | Nat Commun | Volume | 7 |
| Pages | 10574 | PubMed ID | 26868148 |
| Mgi Jnum | J:236274 | Mgi Id | MGI:5805612 |
| Doi | 10.1038/ncomms10574 | Citation | Johmura Y, et al. (2016) SCF(Fbxo22)-KDM4A targets methylated p53 for degradation and regulates senescence. Nat Commun 7:10574 |
| abstractText | Recent evidence has revealed that senescence induction requires fine-tuned activation of p53, however, mechanisms underlying the regulation of p53 activity during senescence have not as yet been clearly established. We demonstrate here that SCF(Fbxo22)-KDM4A is a senescence-associated E3 ligase targeting methylated p53 for degradation. We find that Fbxo22 is highly expressed in senescent cells in a p53-dependent manner, and that SCF(Fbxo22) ubiquitylated p53 and formed a complex with a lysine demethylase, KDM4A. Ectopic expression of a catalytic mutant of KDM4A stabilizes p53 and enhances p53 interaction with PHF20 in the presence of Fbxo22. SCF(Fbxo22)-KDM4A is required for the induction of p16 and senescence-associated secretory phenotypes during the late phase of senescence. Fbxo22(-/-) mice are almost half the size of Fbxo22(+/-) mice owing to the accumulation of p53. These results indicate that SCF(Fbxo22)-KDM4A is an E3 ubiquitin ligase that targets methylated p53 and regulates key senescent processes. |
