Mitotic Disassembly of Nuclear Pore Complexes Involves CDK1- and PLK1-Mediated Phosphorylation of Key Interconnecting Nucleoporins

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.

Keywords: CDK1; NDC1; NPC; NPC disassembly; Nup53; Nup98; PLK1; mitosis; nucleoporin; phosphorylation.

MeSH terms

  • CDC2 Protein Kinase
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism*
  • HeLa Cells
  • Humans
  • Mitosis / physiology*
  • Nuclear Envelope / genetics
  • Nuclear Envelope / metabolism
  • Nuclear Pore / genetics
  • Nuclear Pore / metabolism*
  • Nuclear Pore Complex Proteins / genetics
  • Nuclear Pore Complex Proteins / metabolism*
  • Phosphorylation
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*


  • Cell Cycle Proteins
  • Nuclear Pore Complex Proteins
  • Nup98 protein, human
  • Proto-Oncogene Proteins
  • Protein Serine-Threonine Kinases
  • polo-like kinase 1
  • CDC2 Protein Kinase
  • CDK1 protein, human
  • Cyclin-Dependent Kinases