title: Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and genome stability.
abstract: Temporal regulation of microtubule dynamics is essential for proper progression of mitosis and control of microtubule plus-end tracking proteins by phosphorylation is an essential component of this regulation. Here we show that Aurora B and CDK1 phosphorylate microtubule end-binding protein 2 (EB2) at multiple sites within the amino terminus and a cluster of serine/threonine residues in the linker connecting the calponin homology and end-binding homology domains. EB2 phosphorylation, which is strictly associated with mitotic entry and progression, reduces the binding affinity of EB2 for microtubules. Expression of non-phosphorylatable EB2 induces stable kinetochore microtubule dynamics and delays formation of bipolar metaphase plates in a microtubule binding-dependent manner, and leads to aneuploidy even in unperturbed mitosis. We propose that Aurora B and CDK1 temporally regulate the binding affinity of EB2 for microtubules, thereby ensuring kinetochore microtubule dynamics, proper mitotic progression and genome stability.
authors.affiliation: Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Iimori
authors.affiliation: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Sugiko
authors.initials: S
authors.lastname: Watanabe
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kiyonari
authors.affiliation: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.|Taiho Pharmaceutical Co., Ltd., 224-2, Ebisuno, Hiraishi, Kawauchi-cho, Tokushima 771-0194, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Department of Biochemistry I, Kanazawa Medical University, 1-1 Daigaku Uchinada Kahoku, Ishikawa 920-0293, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Sakasai
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saeki
authors.affiliation: Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Oki
authors.affiliation: Department of Molecular Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.|Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kitao
authors.affiliation: Innovative Anticancer Strategy for Therapeutics and Diagnosis Group, Innovation Center for Medical Redox Navigation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.|Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Maehara
mesh_terms: D064107:Aurora Kinase B / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D016203:CDC2 Protein Kinase; D002460:Cell Line; D018844:Cyclin-Dependent Kinases / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D042822:Genomic Instability; D006801:Humans; D018386:Kinetochores / Q000378:metabolism / Q000648:ultrastructure; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D008938:Mitosis / Q000235:genetics / Q000502:physiology*; D010766:Phosphorylation
chemical_list: C588005:MAPRE2 protein, human; D008869:Microtubule-Associated Proteins; C576921:AURKB protein, human; D064107:Aurora Kinase B; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases