Mitotic Disassembly of Nuclear Pore Complexes Involves CDK1- and PLK1-Mediated Phosphorylation of Key Interconnecting Nucleoporins.
Mitotic Disassembly of Nuclear Pore Complexes Involves CDK1- and PLK1-Mediated Phosphorylation of Key Interconnecting Nucleoporins.
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DOI：
10.1016/j.devcel.2017.08.020
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发表时间：
2017-10-23
影响因子：
11.8
通讯作者：
Kutay U
中科院分区：
文献类型：
--
作者：
Linder MI;Köhler M;Boersema P;Weberruss M;Wandke C;Marino J;Ashiono C;Picotti P;Antonin W;Kutay U
在分裂间期，核膜（NE）作为细胞质和细胞质之间的选择性屏障。当脊椎动物细胞进入有丝分裂时，NE在核膜破裂（NEBD）过程中被拆除。核孔复合物（nuclear pore complex，NPC）的降解是NEBD的一个关键方面，是NE透化和细胞质有丝分裂纺锤体形成所必需的。在这里，我们表明，CDK 1和polo样激酶1（PLK 1）支持有丝分裂NPC解体的过度磷酸化的Nup 98，核孔蛋白的看门人，和Nup 53，中央核孔蛋白连接内部NPC支架孔膜。Nup 53的多位点磷酸化对其从其伴侣核孔蛋白（包括孔膜蛋白NDC 1）中释放至关重要。在半透化细胞中NPC分解的初始步骤可以通过包括细胞周期蛋白B-CDK 1、NIMA和PLK 1的有丝分裂激酶的混合物重建，这表明通过蛋白磷酸化解链核孔蛋白相互作用是有丝分裂NE透化的重要原理。PLK 1在有丝分裂前期定位于NPC并促进NPC的解体CDK 1和PLK 1介导中心连接核孔蛋白Nup 53的过度磷酸化Nup 53的多位点磷酸化促进NPC的解体有丝分裂激酶在重建系统中诱导NPC解体核孔复合物（NPC）的解体是多细胞动物细胞开放有丝分裂开始时核膜破裂的关键过程。Linder等人显示了通过CDK 1和PLK 1对关键互连核孔蛋白Nup 53的多位点磷酸化是中央NPC框架的及时分解所需的。
During interphase, the nuclear envelope (NE) serves as a selective barrier between cytosol and nucleoplasm. When vertebrate cells enter mitosis, the NE is dismantled in the process of nuclear envelope breakdown (NEBD). Disassembly of nuclear pore complexes (NPCs) is a key aspect of NEBD, required for NE permeabilization and formation of a cytoplasmic mitotic spindle. Here, we show that both CDK1 and polo-like kinase 1 (PLK1) support mitotic NPC disintegration by hyperphosphorylation of Nup98, the gatekeeper nucleoporin, and Nup53, a central nucleoporin linking the inner NPC scaffold to the pore membrane. Multisite phosphorylation of Nup53 critically contributes to its liberation from its partner nucleoporins, including the pore membrane protein NDC1. Initial steps of NPC disassembly in semi-permeabilized cells can be reconstituted by a cocktail of mitotic kinases including cyclinB-CDK1, NIMA, and PLK1, suggesting that the unzipping of nucleoporin interactions by protein phosphorylation is an important principle underlying mitotic NE permeabilization. PLK1 localizes to NPCs during prophase and promotes mitotic NPC disassembly CDK1 and PLK1 mediate hyperphosphorylation of the central linker nucleoporin Nup53 Multisite phosphorylation of Nup53 promotes the disintegration of the central NPC Mitotic kinases induce NPC disassembly in a reconstituted system The disassembly of nuclear pore complexes (NPCs) is a key process for nuclear envelope breakdown at the onset of open mitosis in metazoan cells. Linder et al. show that multisite phosphorylation of the key interconnecting nucleoporin Nup53 by CDK1 and PLK1 is required for the timely disassembly of the central NPC framework.
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影响因子：
64.5
作者：
Knockenhauer KE;Schwartz TU
通讯作者：
Schwartz TU
影响因子：
7.3
作者：
Kettenbach AN;Schweppe DK;Faherty BK;Pechenick D;Pletnev AA;Gerber SA
通讯作者：
Gerber SA
影响因子：
16.6
作者：
Haefner, Julia;Mayr, Monika I.;Mayer, Thomas U.
通讯作者：
Mayer, Thomas U.
影响因子：
16.8
作者：
Hoelz, Andre;Glavy, Joseph S.;Beck, Martin
通讯作者：
Beck, Martin
DOI：
10.1126/science.aaf0643
发表时间：
2016-04-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kosinski J;Mosalaganti S;von Appen A;Teimer R;DiGuilio AL;Wan W;Bui KH;Hagen WJ;Briggs JA;Glavy JS;Hurt E;Beck M
通讯作者：
Beck M