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Journal of Virology, October 2001, p. 9799-9807, Vol. 75, No. 20
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.
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

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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.
Present address: Duke University Medical School, Durham, NC 27701.
Present address: Chicago Medical School, North Chicago, IL 60064.
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