title: Trip12 is an E3 ubiquitin ligase for USP7/HAUSP involved in the DNA damage response.
abstract: The deubiquitinating enzyme, USP7/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 USP7 is regulated by the ubiquitin-proteasome pathway. We identified the thyroid hormone receptor interactor 12 (Trip12) as a ubiquitin E3 ligase for USP7. We also found that Trip12 affects USP7-mediated stabilization of p53 and the checkpoint proteins 53BP1 and Chk1. Knockdown of Trip12 leads to an increased cell population in G1 phase, mimicking USP7 overexpression. In contrast, Trip12 overexpression increased the number of cells in intra-S-phase, phenocopying the USP7 knockdown phenotype. Therefore, our data reveal an important modulatory role for Trip12 in the USP7-dependent DNA damage response.
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, China.
authors: Xiaoliang
authors: X
authors: Liu
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, China.
authors: Xiangcai
authors: X
authors: Yang
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, China.|Kunming College of Life Science, University of Chinese Academy of Sciences, China.
authors: Yongxin
authors: Y
authors: Li
authors: Yunnan Population and Family Planning Research Institute, Kunming, China.
authors: Shuhua
authors: S
authors: Zhao
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, China.
authors: Chaocui
authors: C
authors: Li
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, China.
authors: Pengcheng
authors: P
authors: Ma
authors: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, China.
authors: Bingyu
authors: B
authors: Mao
mesh_terms: D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D004249:DNA Damage; D059565:G2 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000076084:Ubiquitin-Specific Peptidase 7; D054875:Ubiquitination; D015854:Up-Regulation
chemical_list: D002352:Carrier Proteins; D016159:Tumor Suppressor Protein p53; C530813:TRIP12 protein, human; D044767:Ubiquitin-Protein Ligases; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D046988:Proteasome Endopeptidase Complex
keywords: DNA damage response; Polyubiquitination; Trip12; USP7; cell cycle