title: ERK Plays a Role in Chromosome Alignment and Participates in M-Phase Progression.
abstract: Cell division, a prerequisite for cell proliferation, is a process in which each daughter cell inherits one complete set of chromosomes. The mitotic spindle is a dedicated apparatus for the alignment and segregation of chromosomes. Extracellular signal-regulated kinase (ERK) 1/2 plays crucial roles in cell cycle progression, particularly during M-phase. Although, association with the mitotic spindle has been reported, the precise roles played by ERK in the dynamics of the mitotic spindle and in M-phase progression remain to be elucidated. In this study, we used MEK inhibitors U0126 and GSK1120212 to dissect the roles of ERK in M-phase progression and chromosome alignment. Fluorescence microscopy revealed that ERK is localized to the spindle microtubules in a manner independent of Src kinase, which is one of the kinases upstream of ERK at mitotic entry. ERK inhibition induces an increase in the number of prophase cells and a decrease in the number of anaphase cells. Time-lapse imaging revealed that ERK inhibition perturbs chromosome alignment, thereby preventing cells from entering anaphase. These results suggest that ERK plays a role in M-phase progression by regulating chromosome alignment and demonstrate one of the mechanisms by which the aberration of ERK signaling may produce cancer cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan.
authors.forename: Erika
authors.initials: E
authors.lastname: Iwamoto
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Ueta
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Matsui
authors.affiliation: Department of Anatomy, Anthropology and Cell Biology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, 980-8575, Japan.
authors.forename: Keiju
authors.initials: K
authors.lastname: Kamijo
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kuga
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan.
authors.forename: Youhei
authors.initials: Y
authors.lastname: Saito
authors.affiliation: Department of Molecular Cell Biology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, 260-8675, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Yamaguchi
authors.affiliation: Department of Biochemistry and Molecular Biology, Kyoto Pharmaceutical University, Kyoto, 607-8414, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakayama
mesh_terms: D000705:Anaphase / Q000187:drug effects; D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D002877:Chromosomes, Human / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D009570:Nitriles / Q000494:pharmacology; D011418:Prophase / Q000187:drug effects; D011728:Pyridones / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology; D008941:Spindle Apparatus / Q000235:genetics* / Q000378:metabolism; D013552:Swine; D059008:Time-Lapse Imaging
chemical_list: D002070:Butadienes; D009570:Nitriles; D011728:Pyridones; D011744:Pyrimidinones; C113580:U 0126; C560077:trametinib; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: CHROMOSOME ALIGNMENT; ERK; GSK1120212; M-PHASE; U0126