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Trip12 is an E3 ubiquitin ligase for USP 7/ HAUSP involved in the DNA damage response
Author(s) -
Liu Xiaoliang,
Yang Xiangcai,
Li Yongxin,
Zhao Shuhua,
Li Chaocui,
Ma Pengcheng,
Mao Bingyu
Publication year - 2016
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12471
Subject(s) - deubiquitinating enzyme , ubiquitin ligase , ubiquitin , gene knockdown , proteasome , microbiology and biotechnology , dna damage , biology , dna ligase , chemistry , dna , biochemistry , gene
The deubiquitinating enzyme, USP 7/ HAUSP (herpesvirus‐associated ubiquitin‐specific protease), is a key regulator of the tumor suppressor p53 and plays a major role in regulating genome stability. Here, we report that the protein stability of USP 7 is regulated by the ubiquitin–proteasome pathway. We identified the thyroid hormone receptor interactor 12 (Trip12) as a ubiquitin E3 ligase for USP 7. We also found that Trip12 affects USP 7‐mediated stabilization of p53 and the checkpoint proteins 53 BP 1 and Chk1. Knockdown of Trip12 leads to an increased cell population in G1 phase, mimicking USP 7 overexpression. In contrast, Trip12 overexpression increased the number of cells in intra‐S‐phase, phenocopying the USP 7 knockdown phenotype. Therefore, our data reveal an important modulatory role for Trip12 in the USP 7‐dependent DNA damage response.