title: Phosphorylation of Nup98 by multiple kinases is crucial for NPC disassembly during mitotic entry.
abstract: Disassembly of nuclear pore complexes (NPCs) is a decisive event during mitotic entry in cells undergoing open mitosis, yet the molecular mechanisms underlying NPC disassembly are unknown. Using chemical inhibition and depletion experiments we show that NPC disassembly is a phosphorylation-driven process, dependent on CDK1 activity and supported by members of the NIMA-related kinase (Nek) family. We identify phosphorylation of the GLFG-repeat nucleoporin Nup98 as an important step in mitotic NPC disassembly. Mitotic hyperphosphorylation of Nup98 is accomplished by multiple kinases, including CDK1 and Neks. Nuclei carrying a phosphodeficient mutant of Nup98 undergo nuclear envelope breakdown slowly, such that both the dissociation of Nup98 from NPCs and the permeabilization of the nuclear envelope are delayed. Together, our data provide evidence for a phosphorylation-dependent mechanism underlying disintegration of NPCs during prophase. Moreover, we identify mitotic phosphorylation of Nup98 as a rate-limiting step in mitotic NPC disassembly.
authors.affiliation: Institute of Biochemistry, ETH Zurich, Switzerland.
authors.forename: Eva
authors.initials: E
authors.lastname: Laurell
authors.forename: Katja
authors.initials: K
authors.lastname: Beck
authors.forename: Ksenia
authors.initials: K
authors.lastname: Krupina
authors.forename: Gandhi
authors.initials: G
authors.lastname: Theerthagiri
authors.forename: Bernd
authors.initials: B
authors.lastname: Bodenmiller
authors.forename: Peter
authors.initials: P
authors.lastname: Horvath
authors.forename: Ruedi
authors.initials: R
authors.lastname: Aebersold
authors.forename: Wolfram
authors.initials: W
authors.lastname: Antonin
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kutay
mesh_terms: D000818:Animals; D001230:Aspergillus / Q000166:cytology; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis; D009154:Mutation; D000072380:NIMA-Related Kinase 1; D009685:Nuclear Envelope / Q000378:metabolism; D022022:Nuclear Pore / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011418:Prophase; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D028861:Nuclear Pore Complex Proteins; C093350:nuclear pore complex protein 98; C000606914:NEK1 protein, human; D000072380:NIMA-Related Kinase 1; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase