| General information | Literature | Expression | Regulation | Mutation | Homolog | Interaction |
Basic Information | |
|---|---|
Gene ID | 23515 |
Name | MORC3 |
Synonymous | MORC family CW-type zinc finger 3;MORC3;MORC family CW-type zinc finger 3 |
Definition | MORC family CW-type zinc finger protein 3|nuclear matrix protein NXP2|zinc finger CW-type coiled-coil domain protein 3|zinc finger, CW type with coiled-coil domain 3|zinc finger, CW-type with coiled-coil domain 3 |
Position | 21q22.13 |
Gene type | protein-coding |
Title | Abstract |
| Dynamic regulation of p53 subnuclear localization and senescence by MORC3. | 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. |