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Journal of Virology, October 2001, p. 9799-9807, Vol. 75, No. 20
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.20.9799-9807.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Overexpression of Simian Virus 40 Small-T Antigen Blocks Centrosome Function and Mitotic Progression in Human Fibroblasts

Stéphanie Gaillard,dagger Kelly M. Fahrbach, Rajini Parkati,Dagger and Kathleen Rundell*

Department of Microbiology-Immunology and the Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, Illinois

Received 5 February 2001/Accepted 25 July 2001

Recombinant adenoviruses that express high levels of the simian virus 40 (SV40) small-t (ST) antigen have been used to study the requirement for ST to drive cell cycle proliferation of confluent human diploid fibroblasts. This occurs when either large-T (LT) antigen or serum is added to provide a second signal. While cells readily completed S phase in these experiments, they were found to accumulate with 4N DNA content. Cellular and nuclear morphology, as well as the biochemical status of cyclin B complexes, showed that these cells entered mitosis but were blocked prior to mitotic metaphase. The defect appears to reflect an inability of cells overexpressing ST to form organized centrosomes that duplicate and separate normally during the cell cycle and, therefore, the absence of a mitotic spindle. The ability of ST to bind protein phosphatase 2A was required for this pattern, suggesting that altered phosphorylation of key centrosomal components may occur when ST is overexpressed. Although the possible significance of ST effects on the centrosome cycle is not fully understood, these findings suggest that ST could influence chromosomal instability patterns that are a hallmark of SV40-transformed cells and LT expression.

* Corresponding author. Mailing address: Department of Microbiology-Immunology, Searle Research Bldg., Mail code S213, Northwestern University, 320 E. Superior St., Chicago, IL 60611-3010. Phone: (312) 503-5917. Fax: (312) 503-1339. E-mail: krundell{at}northwestern.edu.

dagger Present address: Duke University Medical School, Durham, NC 27701.

Dagger Present address: Chicago Medical School, North Chicago, IL 60064.

Journal of Virology, October 2001, p. 9799-9807, Vol. 75, No. 20
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.20.9799-9807.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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