SUMOylated NKAP is essential for chromosome alignment by anchoring CENP-E to kinetochores.
SUMOylated NKAP is essential for chromosome alignment by anchoring CENP-E to kinetochores.
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SUMO 化的 NKAP 通过将 CENP-E 锚定到动粒而对于染色体比对至关重要
DOI：
10.1038/ncomms12969
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发表时间：
2016-10-03
影响因子：
16.6
通讯作者：
Xia, Qing
中科院分区：
文献类型：
--
作者：
Li, Teng;Chen, Liang;Cheng, Juanxian;Dai, Jiang;Huang, Yijiao;Zhang, Jian;Liu, Zhaoshan;Li, Ang;Li, Na;Wang, Hongxia;Yin, Xiaomin;He, Kun;Yu, Ming;Zhou, Tao;Zhang, Xuemin;Xia, Qing
染色体的精确分离需要染色体比对。染色体错配可导致基因组不稳定和肿瘤发生。在这里，我们表明NF-κB激活蛋白（NKAP）通过将CENP-E锚定在动粒上对于染色体比对至关重要。NKAP敲低导致人类细胞中染色体错配和前中期停滞。NKAP动态定位于着丝粒，并且是CENP-E着丝粒定位所需的。NKAP主要在有丝分裂中被SUMO化，并且NKAP结合CENP-E需要SUMO化。NKAP的SUMO化缺陷突变体不能支持CENP-E在动粒上的定位或正确的染色体比对。此外，Bub 3募集NKAP以稳定CENP-E在着丝粒处与BubR 1的结合。重要的是，NKAP表达的缺失导致培养细胞中的非整倍体，并且在人软组织肉瘤中观察到。这些发现表明，NKAP是一种新的和关键的有丝分裂调节，其失调可能有助于肿瘤的发生，引起染色体不稳定。 着丝粒结合的马达CENP-E在染色体排列中起着关键作用。在这里，作者表明，NF-κB激活蛋白（NKAP）动态定位于动粒，在有丝分裂期间被SUMO化，并且这种修饰是NKAP结合CENP-E并将CENP-E定位于动粒所必需的。
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. The kinetochore-bound motor CENP-E plays a critical role in chromosome alignment. Here, the authors show that NF-κB activating protein (NKAP) dynamically localises to kinetochores, is SUMOylated during mitosis, and this modification is required for NKAP to bind CENP-E and localise CENP-E to the kinetochore.
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DOI：
10.1038/nrm3494
发表时间：
2013-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
21.3
作者：
Bakhoum, Samuel F.;Thompson, Sarah L.;Manning, Amity L.;Compton, Duane A.
通讯作者：
Compton, Duane A.
DOI：
10.1038/nrm2718
发表时间：
2009-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
14.9
作者：
Burgute BD;Peche VS;Steckelberg AL;Glöckner G;Gaßen B;Gehring NH;Noegel AA
通讯作者：
Noegel AA
影响因子：
64.5
作者：
Hori, Tetsuya;Amano, Miho;Fukagawa, Tatsuo
通讯作者：
Fukagawa, Tatsuo