論文 - 詳細
| RRC ID | 2428 |
|---|---|
| 著者 | Takahashi K, Yoshida N, Murakami N, Kawata K, Ishizaki H, Tanaka-Okamoto M, Miyoshi J, Zinn AR, Shime H, Inoue N. |
| タイトル | Dynamic regulation of p53 subnuclear localization and senescence by MORC3. |
| ジャーナル | Mol Biol Cell |
| Abstract |
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. |
| 巻・号 | 18(5) |
| ページ | 1701-9 |
| 公開日 | 2007-5-1 |
| DOI | 10.1091/mbc.e06-08-0747 |
| PII | E06-08-0747 |
| PMID | 17332504 |
| PMC | PMC1855011 |
| MeSH | Animals Antigens, Nuclear / metabolism Autoantigens / metabolism Cell Line Cell Nucleus / metabolism Cellular Senescence Cyclin-Dependent Kinase Inhibitor p21 / metabolism Doxorubicin / pharmacology Fibroblasts / cytology Fibroblasts / drug effects Fibroblasts / metabolism Genes, p53 HeLa Cells Humans Mice Mice, Inbred C57BL Mice, Knockout Nuclear Proteins / deficiency Nuclear Proteins / genetics Nuclear Proteins / metabolism* Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Transfection Tumor Suppressor Protein p53 / deficiency Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* |
| IF | 3.791 |
| 引用数 | 52 |
| WOS 分野 | CELL BIOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | WI-38 |