title: Phosphorylation of NuSAP by Cdk1 regulates its interaction with microtubules in mitosis.
abstract: Cell division in eukaryotes depends on a fine control of the dynamic changes of microtubules. Nucleolar and spindle-associated protein (NuSAP) is a microtubule-binding and -bundling protein essential for the integrity of the anaphase spindle and cell division. NuSAP contains two consensus cdk phosphorylation sites in its microtubule-binding domain. Here we show NuSAP is phosphorylated by cdk1 in early mitosis. This phosphorylation inhibits the binding of NuSAP to microtubules. During metaphase-to anaphase transition, NuSAP is dephosphorylated to promote spindle midzone formation and cell cycle progression. Expression of cdk1 phosphorylation-null mutant causes extensive bundling of microtubules in the prometaphase spindle. Our results suggest that phosphorylation and dephosphorylation of NuSAP during progression of mitosis regulate spindle organization through modulation of the dynamics of microtubules.
authors.affiliation: Graduate Institute of Oral Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Han-Yi
authors.initials: HY
authors.lastname: Chou
authors.forename: Ting-Huang
authors.initials: TH
authors.lastname: Wang
authors.forename: Sheng-Chung
authors.initials: SC
authors.lastname: Lee
authors.forename: Pang-Hung
authors.initials: PH
authors.lastname: Hsu
authors.forename: Ming-Daw
authors.initials: MD
authors.lastname: Tsai
authors.forename: Chih-Ling
authors.initials: CL
authors.lastname: Chang
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
mesh_terms: D001665:Binding Sites; D016203:CDC2 Protein Kinase / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000235:genetics / Q000378:metabolism*; D008938:Mitosis; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D054730:Protein Interaction Domains and Motifs; D008941:Spindle Apparatus / Q000235:genetics / Q000378:metabolism; D013912:Threonine / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; C000709213:NUSAP1 protein, human; D013912:Threonine; D016203:CDC2 Protein Kinase