title: TD-60 links RalA GTPase function to the CPC in mitosis.
abstract: TD-60 (also known as RCC2) is a highly conserved protein that structurally resembles the Ran guanine exchange factor (GEF) RCC1, but has not previously been shown to have GEF activity. TD-60 has a typical chromosomal passenger complex (CPC) distribution in mitotic cells, but associates with integrin complexes and is involved in cell motility during interphase. Here we show that TD-60 exhibits GEF activity, in vitro and in cells, for the small GTPase RalA. TD-60 or RalA depletion causes spindle abnormalities in prometaphase associated with abnormal centromeric accumulation of CPC components. TD-60 and RalA apparently work together to contribute to the regulation of kinetochore-microtubule interactions in early mitosis. Importantly, several mitotic phenotypes caused by TD-60 depletion are reverted by the expression of a GTP-locked mutant, RalA (Q72L). The demonstration that a small GTPase participates in the regulation of the CPC reveals a level of mitotic regulation not suspected in previous studies.
authors.affiliation: 1] Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK [2] Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Papini
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Lars
authors.initials: L
authors.lastname: Langemeyer
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Abad
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Alastair
authors.initials: A
authors.lastname: Kerr
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: Itaru
authors.initials: I
authors.lastname: Samejima
authors.affiliation: Department of Biochemistry, Institute of Integrative Biology, University of Liverpool, Crown St, Liverpool L69 7ZB, UK.
authors.forename: Patrick A
authors.initials: PA
authors.lastname: Eyers
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: A Arockia
authors.initials: AA
authors.lastname: Jeyaprakash
authors.affiliation: Institute for Cell and Molecular Biosciences (ICaMB), Newcastle University, Medical School, Framlington Place, Newcastle upon Tyne NE2 4HH, UK.
authors.forename: Jonathan M G
authors.initials: JM
authors.lastname: Higgins
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Francis A
authors.initials: FA
authors.lastname: Barr
authors.affiliation: Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Michael Swann Building, Kings Buildings, Max Born Crescent, Edinburgh EH9 3BF, UK.
authors.forename: William C
authors.initials: WC
authors.lastname: Earnshaw
mesh_terms: D064107:Aurora Kinase B / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D002503:Centromere / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D020090:Chromosome Segregation; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D066298:In Vitro Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism; D008938:Mitosis / Q000235:genetics*; D049468:Prometaphase / Q000235:genetics; D008941:Spindle Apparatus / Q000378:metabolism*; D000077022:Survivin; D020725:ral GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C107489:BIRC5 protein, human; C490157:CDCA8 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D020662:Guanine Nucleotide Exchange Factors; C083767:INCENP protein, human; D051034:Inhibitor of Apoptosis Proteins; C477650:RCC2 protein, human; D000077022:Survivin; C576921:AURKB protein, human; D064107:Aurora Kinase B; C492198:RALA protein, human; D020725:ral GTP-Binding Proteins