title: USP9X regulates centrosome duplication and promotes breast carcinogenesis.
abstract: Defective centrosome duplication is implicated in microcephaly and primordial dwarfism as well as various ciliopathies and cancers. Yet, how the centrosome biogenesis is regulated remains poorly understood. Here we report that the X-linked deubiquitinase USP9X is physically associated with centriolar satellite protein CEP131, thereby stabilizing CEP131 through its deubiquitinase activity. We demonstrate that USP9X is an integral component of centrosome and is required for centrosome biogenesis. Loss-of-function of USP9X impairs centrosome duplication and gain-of-function of USP9X promotes centrosome amplification and chromosome instability. Significantly, USP9X is overexpressed in breast carcinomas, and its level of expression is correlated with that of CEP131 and higher histologic grades of breast cancer. Indeed, USP9X, through regulation of CEP131 abundance, promotes breast carcinogenesis. Our experiments identify USP9X as an important regulator of centrosome biogenesis and uncover a critical role for USP9X/CEP131 in breast carcinogenesis, supporting the pursuit of USP9X/CEP131 as potential targets for breast cancer intervention.
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Song
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Liu
authors.affiliation: Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ding
authors.affiliation: Research Center of Basic Medical Science, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Song
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Shangda
authors.initials: S
authors.lastname: Yang
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Shan
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Su
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Ma
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yu
authors.affiliation: Laboratory of Proteomics, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Yang
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yao
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.|Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Shang
authors.affiliation: 2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Tianjin Key Laboratory of Medical Epigenetics, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.|Tianjin Key Laboratory of Cellular and Molecular Immunology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), Department of Immunology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin 300070, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
mesh_terms: D001943:Breast Neoplasms / Q000378:metabolism*; D063646:Carcinogenesis / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism*; D043171:Chromosomal Instability; D003598:Cytoskeletal Proteins; D005260:Female; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008868:Microtubule Proteins / Q000378:metabolism*; D001678:Organelle Biogenesis; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*
chemical_list: C578334:CEP131 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008868:Microtubule Proteins; C506234:USP9X protein, human; D043222:Ubiquitin Thiolesterase