title: ABRO1 suppresses tumourigenesis and regulates the DNA damage response by stabilizing p53.
abstract: Abraxas brother 1 (ABRO1) has been reported to be a component of the BRISC complex, a multiprotein complex that specifically cleaves 'Lys-63'-linked ubiquitin. However, current knowledge of the functions of ABRO1 is limited. Here we report that ABRO1 is frequently downregulated in human liver, kidney, breast and thyroid gland tumour tissues. Depletion of ABRO1 in cancer cells reduces p53 levels and enhances clone formation and cellular transformation. Conversely, overexpression of ABRO1 suppresses cell proliferation and tumour formation in a p53-dependent manner. We further show that ABRO1 stabilizes p53 by facilitating the interaction of p53 with USP7. DNA-damage induced accumulation of endogenous ABRO1 as well as translocation of ABRO1 to the nucleus, and the induction of p53 by DNA damage is almost completely attenuated by ABRO1 depletion. Our study shows that ABRO1 is a novel p53 regulator that plays an important role in tumour suppression and the DNA damage response.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27-Taiping Road, Beijing 100850, China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Chemical Engineering and Technology, TianJin University, Tianjin 300073, China.
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Cao
authors.affiliation: Department of Liver and Gallbladder Surgery, The General Hospital of Chinese People's Liberation Army, Beijing 100853, China.
authors.forename: Jiahong
authors.initials: J
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27-Taiping Road, Beijing 100850, China.
authors.forename: Changyan
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27-Taiping Road, Beijing 100850, China.
authors.forename: Wangxiang
authors.initials: W
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27-Taiping Road, Beijing 100850, China.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27-Taiping Road, Beijing 100850, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27-Taiping Road, Beijing 100850, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27-Taiping Road, Beijing 100850, China.
authors.forename: Changhui
authors.initials: C
authors.lastname: Ge
authors.affiliation: School of Chemical Engineering and Technology, TianJin University, Tianjin 300073, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Ge
authors.affiliation: 1] State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, 27-Taiping Road, Beijing 100850, China [2] School of Chemical Engineering and Technology, TianJin University, Tianjin 300073, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yang
mesh_terms: D017209:Apoptosis; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D004249:DNA Damage; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D025801:Ubiquitin / Q000378:metabolism; D043222:Ubiquitin Thiolesterase / Q000378:metabolism; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases / Q000378:metabolism*
chemical_list: C577338:ABRAXAS2 protein, human; D034521:Nuclear Matrix-Associated Proteins; D012333:RNA, Messenger; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D025801:Ubiquitin; C464569:USP7 protein, human; D043222:Ubiquitin Thiolesterase; D000076084:Ubiquitin-Specific Peptidase 7; D064570:Ubiquitin-Specific Proteases