Linder Monika I, Köhler Mario, Boersema Paul, Weberruss Marion, Wandke Cornelia, Marino Joseph, Ashiono Caroline, Picotti Paola, Antonin Wolfram, Kutay Ulrike
Institute of Biochemistry, Department of Biology, ETH Zurich, 8093 Zurich, Switzerland.
Institute of Biochemistry and Molecular Cell Biology, Medical School, RWTH Aachen University, 52074 Aachen, Germany.
Dev Cell. 2017 Oct 23;43(2):141-156.e7. doi: 10.1016/j.devcel.2017.08.020.
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.
在间期，核膜（NE）作为细胞质和核质之间的选择性屏障。当脊椎动物细胞进入有丝分裂时，核膜在核膜破裂（NEBD）过程中被解体。核孔复合体（NPCs）的解体是NEBD的一个关键方面，是核膜通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，细胞周期蛋白依赖性激酶1（CDK1）和polo样激酶1（PLK1）都通过对核孔蛋白Nup98（守门核孔蛋白）和Nup53（连接内核孔复合体支架与孔膜的中央核孔蛋白）进行过度磷酸化来支持有丝分裂期NPC的解体。Nup53的多位点磷酸化对其从包括孔膜蛋白NDC1在内的伙伴核孔蛋白中释放起着关键作用。在半透性细胞中，NPC解体的初始步骤可以通过包括细胞周期蛋白B-CDK1、NIMA和PLK1在内的有丝分裂激酶混合物来重建，这表明通过蛋白质磷酸化解开核孔蛋白相互作用是有丝分裂期核膜通透化的一个重要原则。
