Acetylation of Nup62 by TIP60 ensures accurate chromosome segregation in mitosis.
Acetylation of Nup62 by TIP60 ensures accurate chromosome segregation in mitosis.
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DOI：
10.1093/jmcb/mjac056
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发表时间：
2022-12-26
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
在细胞分裂过程中遗传信息的稳定传递需要忠实的有丝分裂纺锤体组装和染色体分离。在真核细胞中，核膜破裂（NEBD）是正确的染色体分离所必需的。尽管有一系列有丝分裂激酶与NEBD有关，但它们如何协调其活性以溶解核被膜和蛋白质机制（如核孔复合物）尚不清楚。在这里，我们确定了一种调节机制，其中Nup 62在人类细胞分裂中被TIP 60乙酰化。Nup 62是TIP 60的一种新的底物，TIP 60对Lys 432的乙酰化作用使核孔蛋白Nup 62-Nup 58-Nup 54复合物在进入有丝分裂过程中溶解。重要的是，这种乙酰化引起的核孔蛋白复合物的重塑促进了Nup 62向有丝分裂纺锤体的分布，这对于协调正确的纺锤体方向是必不可少的。此外，Nup 62的抑制会扰乱有丝分裂期间染色体的准确分离。这些结果建立了一个以前未表征的监管机制，其中TIP 60引起的核孔蛋白动力学促进有丝分裂中的染色体分离。
Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. In eukaryotic cells, nuclear envelope breakdown (NEBD) is required for proper chromosome segregation. Although a list of mitotic kinases has been implicated in NEBD, how they coordinate their activity to dissolve the nuclear envelope and protein machinery such as nuclear pore complexes was unclear. Here, we identified a regulatory mechanism in which Nup62 is acetylated by TIP60 in human cell division. Nup62 is a novel substrate of TIP60, and the acetylation of Lys432 by TIP60 dissolves nucleoporin Nup62–Nup58–Nup54 complex during entry into mitosis. Importantly, this acetylation-elicited remodeling of nucleoporin complex promotes the distribution of Nup62 to the mitotic spindle, which is indispensable for orchestrating correct spindle orientation. Moreover, suppression of Nup62 perturbs accurate chromosome segregation during mitosis. These results establish a previously uncharacterized regulatory mechanism in which TIP60-elicited nucleoporin dynamics promotes chromosome segregation in mitosis.
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影响因子：
4
作者：
Kisurina-Evgenieva, O;Mack, G;Compton, DA
通讯作者：
Compton, DA
影响因子：
5.3
作者：
Bailer, SM;Balduf, C;Hurt, E
通讯作者：
Hurt, E
DOI：
10.1073/pnas.0506345103
发表时间：
2006-02-14
影响因子：
11.1
作者：
Devos, D;Dokudovskaya, S;Sali, A
通讯作者：
Sali, A
影响因子：
7.5
作者：
Krupina K;Goginashvili A;Cleveland DW
通讯作者：
Cleveland DW
影响因子：
11.8
作者：
Linder MI;Köhler M;Boersema P;Weberruss M;Wandke C;Marino J;Ashiono C;Picotti P;Antonin W;Kutay U
通讯作者：
Kutay U