title: Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1.
abstract: The mitotic spindle checkpoint protein Bub1 has been found to be mutated at low frequency in certain human cancers characterized by aneuploidy. Simian virus 40 large T antigen efficiently immortalizes rodent cells and occasionally transforms them to tumorigenicity. T antigen can also cause genomic instability, inducing chromosomal aberrations and aneuploidy. Here, we report an interaction between Bub1 and T antigen. T antigen coimmunoprecipitates with endogenous Bub1 and Bub3, another component of the spindle checkpoint complex. Genetic analysis demonstrates that the interaction of T antigen with Bub1 is not required for immortalization but is closely correlated with transformation. T antigen induces an override of the spindle checkpoint dependent on Bub1 binding. This interaction with proteins of the spindle checkpoint machinery suggests another role for T antigen and provides insight into its ability to cause chromosomal aberrations, aneuploidy, and transformation.
authors.affiliation: Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, Courtauld Building, 91 Riding House Street, London W1W 7BS, United Kingdom.
authors.forename: Marina
authors.initials: M
authors.lastname: Cotsiki
authors.forename: Rowena L
authors.initials: RL
authors.lastname: Lock
authors.forename: Yuan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Grace L
authors.initials: GL
authors.lastname: Williams
authors.forename: Jean
authors.initials: J
authors.lastname: Zhao
authors.forename: David
authors.initials: D
authors.lastname: Perera
authors.forename: Raimundo
authors.initials: R
authors.lastname: Freire
authors.forename: Alan
authors.initials: A
authors.lastname: Entwistle
authors.forename: Erica A
authors.initials: EA
authors.lastname: Golemis
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Roberts
authors.forename: Parmjit S
authors.initials: PS
authors.lastname: Jat
authors.forename: Ole V
authors.initials: OV
authors.lastname: Gjoerup
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques
chemical_list: D000952:Antigens, Polyomavirus Transforming; D011494:Protein Kinases; C584277:BUB1 protein, human; C584281:Bub1 protein, mouse; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases