Simian virus 40 large T antigen targets the spindle assembly checkpoint protein Bub1.
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.
Cotsiki
Marina
M
Ludwig Institute for Cancer Research, Royal Free and University College School of Medicine, Courtauld Building, 91 Riding House Street, London W1W 7BS, United Kingdom.
Lock
Rowena L
RL
Cheng
Yuan
Y
Williams
Grace L
GL
Zhao
Jean
J
Perera
David
D
Freire
Raimundo
R
Entwistle
Alan
A
Golemis
Erica A
EA
Roberts
Thomas M
TM
Jat
Parmjit S
PS
Gjoerup
Ole V
OV
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
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