title: Reduced levels of Dusp3/Vhr phosphatase impair normal spindle bipolarity in an Erk1/2 activity-dependent manner.
abstract: Dual specificity phosphatase-3 (Dusp3/Vhr) regulates cell cycle progression by counteracting the effects of mitogen-activated protein kinases (Mapk) Erk1/2 and Jnk. Despite the known upregulation of Dusp3 at M phase in mammalian cells, its mitotic functions are poorly characterized. Here, we report that loss of Dusp3 by RNAi leads to the formation of multipolar spindles in human mitotic cancer cells in an Erk1/2-dependent manner. In the phosphatase-silenced cells, the normal bipolar spindle structure was restored by chemical inhibition of Erk1/2 and ectopic overexpression of Dusp3. We propose that at M phase Dusp3 keeps Erk1/2 activity in check to facilitate normal mitosis.
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Finland.|Centre for Biotechnology, University of Turku, Finland.|Drug Research Doctoral Programme and FinPharma Doctoral Program Drug Discovery, University of Turku, Finland.
authors.forename: Mahesh Balasaheb
authors.initials: MB
authors.lastname: Tambe
authors.affiliation: Department of Medical Biochemistry and Genetics, Institute of Biomedicine, University of Turku, Finland.
authors.forename: Elli
authors.initials: E
authors.lastname: Narvi
authors.affiliation: Department of Physiology, Institute of Biomedicine, University of Turku, Finland.|Centre for Biotechnology, University of Turku, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Kallio
mesh_terms: D002453:Cell Cycle / Q000235:genetics; D016764:Cell Polarity / Q000235:genetics*; D054640:Dual Specificity Phosphatase 3 / Q000096:biosynthesis / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006367:HeLa Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics; D020935:MAP Kinase Signaling System / Q000235:genetics; D008938:Mitosis / Q000235:genetics*; D010766:Phosphorylation; D034622:RNA Interference; D008941:Spindle Apparatus / Q000235:genetics*; D014162:Transfection
chemical_list: D048670:MAP Kinase Kinase 4; C517025:DUSP3 protein, human; D054640:Dual Specificity Phosphatase 3
keywords: Dusp3; Erk1/2; mitosis; multipolarity; spindle