| Title | The deubiquitinating enzyme complex BRISC regulates Aurora B activation via lysine-63-linked ubiquitination in mitosis |
| Authors | Li, Qin Ma, Yanfang Chang, Fen Xu, Yongjie Deng, Jingcheng Duan, Junyi Jiang, Wei He, Qihua Xu, Luzheng Zhong, Lijun Shao, Genze Li, Li |
| Affiliation | Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Cell Biol, Beijing 100191, Peoples R China Peking Univ, Sch Basic Med Sci, Dept Biochem & Biophys, Hlth Sci Ctr, Beijing 100191, Peoples R China Peking Univ, Ctr Med & Hlth Anal, Hlth Sci Ctr, Beijing 100191, Peoples R China |
| Keywords | KINETOCHORE-MICROTUBULE ATTACHMENTS BRCA1 INCENP OVEREXPRESSION PROGRESSION EXPRESSION RESISTANCE SURVIVIN BRCC36 POOR |
| Issue Date | 6-Dec-2022 |
| Publisher | COMMUNICATIONS BIOLOGY |
| Abstract | Faithful chromosome segregation requires bi-oriented kinetochore-microtubule attachment on the metaphase spindle. Aurora B kinase, the catalytic core of the chromosome passage complex (CPC), plays a crucial role in this process. Aurora B activation has widely been investigated in the context of protein phosphorylation. Here, we report that Aurora B is ubiquitinated in mitosis through lysine-63 ubiquitin chains (K63-Ub), which is required for its activation. Mutation of Aurora B at its primary K63 ubiquitin site inhibits its activation, reduces its kinase activity, and disrupts the association of Aurora B with other components of CPC, leading to severe mitotic defects and cell apoptosis. Moreover, we identify that BRCC36 isopeptidase complex (BRISC) is the K63-specific deubiquitinating enzyme for Aurora B. BRISC deficiency augments the accumulation of Aurora B K63-Ubs, leading to Aurora B hyperactivation and erroneous chromosome-microtubule attachments. These findings define the role of K63-linked ubiquitination in regulating Aurora B activation and provide a potential site for Aurora B-targeting drug design. |
| URI | http://hdl.handle.net/20.500.11897/667646 |
| DOI | 10.1038/s42003-022-04299-4 |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 |
