SUMOylated NKAP is essential for chromosome alignment by anchoring CENP-E to kinetochores

Teng Li, Liang Chen, Juanxian Cheng, Jiang Dai, Yijiao Huang, Jian Zhang, Zhaoshan Liu, Ang Li, Na Li, Hongxia Wang, Xiaomin Yin, Kun He, Ming Yu, Tao Zhou, Xuemin Zhang () and Qing Xia ()
Additional contact information
Teng Li: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Liang Chen: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Juanxian Cheng: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Jiang Dai: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Yijiao Huang: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Jian Zhang: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Zhaoshan Liu: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Ang Li: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Na Li: Affiliated Hospital of Academy of Military Medical Sciences
Hongxia Wang: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Xiaomin Yin: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Kun He: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Ming Yu: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Tao Zhou: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Xuemin Zhang: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis
Qing Xia: State Key Laboratory of Proteomics, Institute of Basic Medical Sciences, National Center of Biomedical Analysis

Nature Communications, 2016, vol. 7, issue 1, 1-14

Abstract: Abstract Chromosome alignment is required for accurate chromosome segregation. Chromosome misalignment can result in genomic instability and tumorigenesis. Here, we show that NF-κB activating protein (NKAP) is critical for chromosome alignment through anchoring CENP-E to kinetochores. NKAP knockdown causes chromosome misalignment and prometaphase arrest in human cells. NKAP dynamically localizes to kinetochores, and is required for CENP-E kinetochore localization. NKAP is SUMOylated predominantly in mitosis and the SUMOylation is needed for NKAP to bind CENP-E. A SUMOylation-deficient mutant of NKAP cannot support the localization of CENP-E on kinetochores or proper chromosome alignment. Moreover, Bub3 recruits NKAP to stabilize the binding of CENP-E to BubR1 at kinetochores. Importantly, loss of NKAP expression causes aneuploidy in cultured cells, and is observed in human soft tissue sarcomas. These findings indicate that NKAP is a novel and key regulator of mitosis, and its dysregulation might contribute to tumorigenesis by causing chromosomal instability.

Date: 2016
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DOI: 10.1038/ncomms12969

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