USP10 regulates p53 localization and stability by deubiquitinating p53 (Cell, 2010, 140:1-13)

報告日期: 2010/04/30
報告時間: 16:00/16:50
報告學生: 許哲裕(英文報告)
講評老師: 洪建中

USP10 regulates p53 localization and stability by deubiquitinating p53


Jian Yuan, Kuntian Luo, Lizhi Zhang, John C. Cheville, and Zhenkun Lou


Cell. 2010 Feb 5;140(3):384-96.


Speaker: 許哲裕

Commentator: 洪建中 老師

Date: Apr. 30, 2010. 4:00-4:50

Place: 602R



p53 is an crucial tumor suppressor that is mutated in more than 50% of human cancers. Its major function is regulating cell fate after cellular stress and repressing the propagation of damaged cell. p53 activity, expression, and localization are mainly regulated by posttranslational modifications, such as phosphorylation, acetylation, and ubiquitination. Mdm2-mediated ubiquitination is the major regulatory mechanism of p53, and induces p53 nuclear export for degradation [1]. In addition, the ubiquitin-specific protease HAUSP mainly localizes in the nucleus, and has been shown to deubiquitinate p53 [2]. However, it is unclear whether ubiquitinated cytoplasmic p53 can be recycled. Here, authors report that USP10, a cytoplasmic ubiquitin-specific protease, deubiquitinates p53, reversing Mdm2-induced p53 nuclear export and degradation.

In the beginning, authors proved that USP10 interacted with p53 by stabilization and deubiquitination. Next, they showed that USP10 was the cytoplasmic p53 deubiquitinase counteracting Mdm2's action and inducing p53 translocation from the cytoplasm back to the nucleus. Furthermore, they saw that USP10 regulated p53-dependent transcriptional activity, cell transformation, and apoptosis. Besides, USP10 was upregulated and translocated to the nucleus after DNA damage and regulated p53-dependent DNA damage response. Finally, authors found that USP10 phosphorylation by ATM regulated its stabilization, translocation, and p53 activation after DNA damage. They also examined the expression of USP10 in renal cell carcinoma (RCC), and got that in cancer cells with WT p53, USP10 acted as a tumor suppressor. On the other hand, in cancer cells owning mutant p53, USP10 could promote tumorous growth. Overall, this study tells us that USP10 is a deubiquitinase for p53, and plays an important role in cancer biology.



1.   Brooks, C.L., and Gu, W. (2006). p53 ubiquitination: Mdm2 and beyond. Mol. Cell 21, 307–315.

2.   Brooks, C.L., Li, M., Hu, M., Shi, Y., and Gu, W. (2007). The p53-Mdm2-HAUSP complex is involved in p53 stabilization by HAUSP. Oncogene 26, 7262–7266.