2. Academic Validation
  3. The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells

The deubiquitinating enzyme complex BRISC is required for proper mitotic spindle assembly in mammalian cells

  • J Cell Biol. 2015 Jul 20;210(2):209-24. doi: 10.1083/jcb.201503039.
Kaowen Yan 1,  Li Li 2,  Xiaojian Wang 3,  Ruisha Hong 4,  Ying Zhang 2,  Hua Yang 2,  Ming Lin 2,  Sha Zhang 2,  Qihua He 5,  Duo Zheng 6,  Jun Tang 3,  Yuxin Yin 7,  Genze Shao 8
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China.
  • 3 State Key Laboratory of Agrobiotechnology, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
  • 4 Department of Cell Biology, School of Basic Medical Sciences, Peking University, Beijing 100191, China School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, China.
  • 5 Center of Medical and Health Analysis, Peking University, Beijing 100191, China.
  • 6 School of Medicine, Shenzhen University, Shenzhen, Guangdong 518060, China.
  • 7 Institute of Systems Biomedicine, Beijing Key Laboratory of Tumor Systems Biology, Peking University, Beijing 100191, China.
  • 8 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.
PMID: 26195665 DOI: 10.1083/jcb.201503039
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.

Figures