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Journal of Virology, April 1999, p. 3102-3107, Vol. 73, No. 4
Department of Microbiology-Immunology and
Robert H. Lurie Comprehensive Cancer Center, Northwestern
University, Chicago, Illinois 60611
Received 25 September 1998/Accepted 15 December 1998
Focus formation in human diploid fibroblasts (HDF cells) is known
to require both the simian virus 40 (SV40) large-T and small-t antigens. Similarly, both SV40 proteins were required to stimulate confluent, density-arrested HDF cells to reenter the cell cycle. This
study used defective recombinant adenoviruses to examine the roles of
the individual SV40 proteins in altering specific steps in the cell
cycle. Small-t antigen and, to a lesser extent, large-T antigen
increased the level of the S phase cyclin cyclin A but without
increasing the activity of associated cyclin kinases unless the two
SV40 proteins were coexpressed. The absence of kinase activity
reflected the presence in density-arrested cells of high levels of the
cyclin-dependent kinase inhibitors p21WAF1 and
p27KIP1. We report here that expression of SV40 large-T
antigen reduced levels of p21WAF1, while expression of
small-t antigen was required to decrease p27KIP1. The
separate effects of large-T and small-t antigens on these two
inhibitors may explain the joint requirement for the two proteins to
drive cell cycle reentry of HDF cells and ultimately transform these cells.
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
The Simian Virus 40 Small-t and Large-T Antigens
Jointly Regulate Cell Cycle Reentry in Human Fibroblasts
*
Corresponding author. Mailing address: Department of
Microbiology-Immunology and The Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 303 E. Chicago Ave., Chicago, IL
60611. Phone: (312) 503-5917. Fax: (312) 908-1372. E-mail: krundell{at}nwu.edu.
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