LUBAC controls chromosome alignment by targeting CENP-E to attached kinetochores

Min Wu, Yan Chang, Huaibin Hu, Rui Mu, Yucheng Zhang, Xuanhe Qin, Xiaotao Duan, Weihua Li, Haiqing Tu, Weina Zhang, Guang Wang, Qiuying Han, Ailing Li, Tao Zhou, Kazuhiro Iwai, Xuemin Zhang () and Huiyan Li ()
Additional contact information
Min Wu: National Center of Biomedical Analysis
Yan Chang: National Center of Biomedical Analysis
Huaibin Hu: National Center of Biomedical Analysis
Rui Mu: Chinese Academy of Medical Sciences and Peking Union Medical College
Yucheng Zhang: National Center of Biomedical Analysis
Xuanhe Qin: National Center of Biomedical Analysis
Xiaotao Duan: Beijing Institute of Pharmacology and Toxicology
Weihua Li: National Center of Biomedical Analysis
Haiqing Tu: National Center of Biomedical Analysis
Weina Zhang: National Center of Biomedical Analysis
Guang Wang: National Center of Biomedical Analysis
Qiuying Han: National Center of Biomedical Analysis
Ailing Li: National Center of Biomedical Analysis
Tao Zhou: National Center of Biomedical Analysis
Kazuhiro Iwai: Kyoto University
Xuemin Zhang: National Center of Biomedical Analysis
Huiyan Li: National Center of Biomedical Analysis

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Faithful chromosome segregation requires proper chromosome congression at prometaphase and dynamic maintenance of the aligned chromosomes at metaphase. Chromosome missegregation can result in aneuploidy, birth defects and cancer. The kinetochore-bound KMN network and the kinesin motor CENP-E are critical for kinetochore-microtubule attachment and chromosome stability. The linear ubiquitin chain assembly complex (LUBAC) attaches linear ubiquitin chains to substrates, with well-established roles in immune response. Here, we identify LUBAC as a key player of chromosome alignment during mitosis. LUBAC catalyzes linear ubiquitination of the kinetochore motor CENP-E, which is specifically required for the localization of CENP-E at attached kinetochores, but not unattached ones. KNL1 acts as a receptor of linear ubiquitin chains to anchor CENP-E at attached kinetochores in prometaphase and metaphase. Thus, linear ubiquitination promotes chromosome congression and dynamic chromosome alignment by coupling the dynamic kinetochore microtubule receptor CENP-E to the static one, the KMN network.

Date: 2019
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DOI: 10.1038/s41467-018-08043-7

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