| First Author | Takahashi K | Year | 2007 |
| Journal | Mol Biol Cell | Volume | 18 |
| Issue | 5 | Pages | 1701-9 |
| PubMed ID | 17332504 | Mgi Jnum | J:127492 |
| Mgi Id | MGI:3763815 | Doi | 10.1091/mbc.E06-08-0747 |
| Citation | Takahashi K, et al. (2007) Dynamic regulation of p53 subnuclear localization and senescence by MORC3. Mol Biol Cell 18(5):1701-9 |
| abstractText | The tumor suppressor p53 is a key transcriptional factor regulating the induction of cellular senescence by oncogenic signals. The activity of p53 is regulated by recruitment into promyelocytic leukemia (PML)-nuclear bodies (NBs) as well as by stabilization through posttranslational modifications such as phosphorylation and acetylation. Here we found that MORC3 (microrchidia3)-ATPase activated p53 and induced cellular senescence in normal human and mouse fibroblasts but not p53-/- fibroblasts. Conversely, genotoxic stress-induced phosphorylation and stabilization of p53 but barely increased its transcriptional activity in Morc3-/- fibroblasts. MORC3 localized on PML-NBs in presence of PML and mediated recruitment of p53 and CREB-binding protein (CBP) into PML-NBs. In contrast, expression of ATPase activity-deficient mutant MORC3-E35A or siRNA repression of MORC3 impaired the localization of p53 and Sp100 but not CBP on PML-NBs. These results suggest that MORC3 regulates p53 activity and localization into PML-NBs. We identified a new molecular mechanism that regulates the activity of nuclear proteins by localization to a nuclear subdomain. |
