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

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.

SUBMITTER: Li T 

PROVIDER: S-EPMC5064014 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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

Li Teng T   Chen Liang L   Cheng Juanxian J   Dai Jiang J   Huang Yijiao Y   Zhang Jian J   Liu Zhaoshan Z   Li Ang A   Li Na N   Wang Hongxia H   Yin Xiaomin X   He Kun K   Yu Ming M   Zhou Tao T   Zhang Xuemin X   Xia Qing Q  

Nature communications 20161003

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 mito  ...[more]