title: The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells.
abstract: Deubiquitinating enzymes (DUBs) negatively regulate protein ubiquitination and play an important role in diverse physiological processes, including mitotic division. The BRCC36 isopeptidase complex (BRISC) is a DUB that is specific for lysine 63-linked ubiquitin hydrolysis; however, its biological function remains largely undefined. Here, we identify a critical role for BRISC in the control of mitotic spindle assembly in cultured mammalian cells. BRISC is a microtubule (MT)-associated protein complex that predominantly localizes to the minus ends of K-fibers and spindle poles and directly binds to MTs; importantly, BRISC promotes the assembly of functional bipolar spindle by deubiquitinating the essential spindle assembly factor nuclear mitotic apparatus (NuMA). The deubiquitination of NuMA regulates its interaction with dynein and importin-β, which are required for its function in spindle assembly. Collectively, these results uncover BRISC as an important regulator of the mitotic spindle assembly and cell division, and have important implications for the development of anticancer drugs targeting BRISC.
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.
authors.forename: Kaowen
authors.initials: K
authors.lastname: Yan
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Xiaojian
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, China.
authors.forename: Ruisha
authors.initials: R
authors.lastname: Hong
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Lin
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Center of Medical and Health Analysis, Peking University, Beijing 100191, China.
authors.forename: Qihua
authors.initials: Q
authors.lastname: He
authors.affiliation: School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Tang
authors.affiliation: Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China gzshao@bjmu.edu.cn lily@bjmu.edu.cn.
authors.forename: Genze
authors.initials: G
authors.lastname: Shao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D034961:Antigens, Nuclear / Q000378:metabolism; D018797:Cell Cycle Proteins; D000072017:Deubiquitinating Enzymes; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D059566:M Phase Cell Cycle Checkpoints; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009097:Multienzyme Complexes / Q000502:physiology*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport; D008941:Spindle Apparatus / Q000378:metabolism*; D064570:Ubiquitin-Specific Proteases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
chemical_list: C577338:ABRAXAS2 protein, human; D048868:Adaptor Proteins, Signal Transducing; D034961:Antigens, Nuclear; C540398:BABAM1 protein, human; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D009097:Multienzyme Complexes; C050045:NUMA1 protein, human; D034521:Nuclear Matrix-Associated Proteins; C518017:BRCC3 protein, human; D000072017:Deubiquitinating Enzymes; D064570:Ubiquitin-Specific Proteases