title: The Ski Protein is Involved in the Transformation Pathway of Aurora Kinase A.
abstract: Oncogenic kinase Aurora A (AURKA) has been found to be overexpresed in several tumors including colorectal, breast, and hematological cancers. Overexpression of AURKA induces centrosome amplification and aneuploidy and it is related with cancer progression and poor prognosis. Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life. Reduced levels of Ski resulted in centrosomes amplification and multipolar spindles formation, same as AURKA overexpressing cells. Importantly, overexpression of Ski wild type, but not S326D and S383D mutants inhibited centrosome amplification and cellular transformation induced by AURKA. Altogether, these results suggest that the Ski protein is a target in the transformation pathway mediated by the AURKA oncogene.
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors.forename: Solange
authors.initials: S
authors.lastname: Rivas
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.|Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Armisén
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors.forename: Diego A
authors.initials: DA
authors.lastname: Rojas
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors.forename: Edio
authors.initials: E
authors.lastname: Maldonado
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors.forename: Hernán
authors.initials: H
authors.lastname: Huerta
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.|Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors.forename: Julio C
authors.initials: JC
authors.lastname: Tapia
authors.affiliation: Department of Pathology, UC-Center for Investigational Oncology (CITO), School of Medicine, Pontificia Universidad Católica de Chile 8330034, Santiago, Chile.
authors.forename: Jaime
authors.initials: J
authors.lastname: Espinoza
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.|Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors.forename: Alicia
authors.initials: A
authors.lastname: Colombo
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.|Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.|Millenium Institute of Immunology and Immunotherapy, Santiago, Chile.
authors.forename: Luis
authors.initials: L
authors.lastname: Michea
authors.affiliation: Department of Microbiology and Molecular Genetics, Stony Brook University, Stony Brook, New York 11794.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hayman
authors.affiliation: Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.|Centro de Investigación y Tratamiento del Cáncer, Facultad de Medicina, Universidad de Chile, Independencia 1027, Santiago, Chile.
authors.forename: Katherine
authors.initials: K
authors.lastname: Marcelain
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D064096:Aurora Kinase A / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; C060614:SKI protein, human; C576917:AURKA protein, human; D064096:Aurora Kinase A
keywords: AURKA; AURORA KINASE; CENTROSOME AMPLIFICATION; Ski