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Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization

Author

Listed:
  • Muyang Li

    (Columbia University
    Columbia University)

  • Delin Chen

    (Columbia University
    Columbia University)

  • Ariel Shiloh

    (Columbia University
    Columbia University)

  • Jianyuan Luo

    (Columbia University
    Columbia University)

  • Anatoly Y. Nikolaev

    (Columbia University
    Columbia University)

  • Jun Qin

    (Baylor College of Medicine)

  • Wei Gu

    (Columbia University
    Columbia University)

Abstract

The p53 tumour suppressor is a short-lived protein that is maintained at low levels in normal cells by Mdm2-mediated ubiquitination and subsequent proteolysis1,2,3. Stabilization of p53 is crucial for its tumour suppressor function1,2,3,4,5. However, the precise mechanism by which ubiquitinated p53 levels are regulated in vivo is not completely understood. By mass spectrometry of affinity-purified p53-associated factors, we have identified herpesvirus-associated ubiquitin-specific protease6 (HAUSP) as a novel p53-interacting protein. HAUSP strongly stabilizes p53 even in the presence of excess Mdm2, and also induces p53-dependent cell growth repression and apoptosis. Significantly, HAUSP has an intrinsic enzymatic activity that specifically deubiquitinates p53 both in vitro and in vivo. In contrast, expression of a catalytically inactive point mutant of HAUSP in cells increases the levels of p53 ubiquitination and destabilizes p53. These findings reveal an important mechanism by which p53 can be stabilized by direct deubiquitination and also imply that HAUSP might function as a tumour suppressor in vivo through the stabilization of p53.

Suggested Citation

  • Muyang Li & Delin Chen & Ariel Shiloh & Jianyuan Luo & Anatoly Y. Nikolaev & Jun Qin & Wei Gu, 2002. "Deubiquitination of p53 by HAUSP is an important pathway for p53 stabilization," Nature, Nature, vol. 416(6881), pages 648-653, April.
  • Handle: RePEc:nat:nature:v:416:y:2002:i:6881:d:10.1038_nature737
    DOI: 10.1038/nature737
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    Cited by:

    1. Qiuhong Zhu & Panpan Liang & Hao Meng & Fangzhen Li & Wei Miao & Cuiying Chu & Wei Wang & Dongxue Li & Cong Chen & Yu Shi & Xingjiang Yu & Yifang Ping & Chaoshi Niu & Hai-bo Wu & Aili Zhang & Xiu-wu B, 2024. "Stabilization of Pin1 by USP34 promotes Ubc9 isomerization and protein sumoylation in glioma stem cells," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    2. Liu Yongganmg & Gao Shizheng, 2010. "A novel porcine gene, USP7, differentially expressed in the musculus longissimus from Wujin and Large White pigs," Czech Journal of Animal Science, Czech Academy of Agricultural Sciences, vol. 55(1), pages 37-41.
    3. Hanlin Lu & Peidong Yuan & Xiaoping Ma & Xiuxin Jiang & Shaozhuang Liu & Chang Ma & Sjaak Philipsen & Qunye Zhang & Jianmin Yang & Feng Xu & Cheng Zhang & Yun Zhang & Wencheng Zhang, 2023. "Angiotensin-converting enzyme inhibitor promotes angiogenesis through Sp1/Sp3-mediated inhibition of notch signaling in male mice," Nature Communications, Nature, vol. 14(1), pages 1-17, December.

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