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

Author

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  • 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)

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.

Suggested Citation

  • 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 & Qing Xia, 2016. "SUMOylated NKAP is essential for chromosome alignment by anchoring CENP-E to kinetochores," Nature Communications, Nature, vol. 7(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12969
    DOI: 10.1038/ncomms12969
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    Cited by:

    1. Ting Li & Dingyi Lu & Chengcheng Yao & Tingting Li & Hua Dong & Zhan Li & Guang Xu & Jiayi Chen & Hao Zhang & Xiaoyu Yi & Haizhen Zhu & Guangqin Liu & Kaiqing Wen & Haixin Zhao & Jun Gao & Yakun Zhang, 2022. "Kansl1 haploinsufficiency impairs autophagosome-lysosome fusion and links autophagic dysfunction with Koolen-de Vries syndrome in mice," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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