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Deubiquitylase OTUD3 Regulates PTEN Stability and Suppresses Tumorigenesis

Deubiquitylase OTUD3 Regulates PTEN Stability and Suppresses Tumorigenesis

Lin Yuan, Yanrong Lv, Hongchang Li, Haidong Gao, Shanshan Song, Yuan Zhang, Guichun Xing, Xiangzhen Kong, Lijing Wang, Yang Li, Tao Zhou, Daming Gao, Zhi-Xiong Xiao, Yuxin Yin, Wenyi Wei, Fuchu He, Lingqiang Zhang

Nat Cell Biol. 2015 Sep;17(9):1169-81.

PMID: 26280536

Abstract:

PTEN is one of the most frequently mutated tumour suppressors and reduction in PTEN protein stability also plays a role in tumorigenesis. Although several ubiquitin ligases for PTEN have been identified, the deubiquitylase for de-polyubiquitylation and stabilization of PTEN is less defined. Here, we report OTUD3 as a deubiquitylase of PTEN. OTUD3 interacts with, de-polyubiquitylates and stabilizes PTEN. Depletion of OTUD3 leads to the activation of Akt signalling, induction of cellular transformation and cancer metastasis. OTUD3 transgenic mice exhibit higher levels of the PTEN protein and are less prone to tumorigenesis. Reduction of OTUD3 expression, concomitant with decreased PTEN abundance, correlates with human breast cancer progression. Furthermore, we identified loss-of-function OTUD3 mutations in human cancers, which either abolish OTUD3 catalytic activity or attenuate the interaction with PTEN. These findings demonstrate that OTUD3 is an essential regulator of PTEN and that the OTUD3-PTEN signalling axis plays a critical role in tumour suppression.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4247097	PTEN human			Price

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