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Journal of Virology, November 1999, p. 9266-9273, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Binding of Polyomavirus Small T Antigen to Protein Phosphatase 2A Is Required for Elimination of p27 and Support of S-Phase Induction in Concert with Large T Antigen

Stefan Schüchner and Erhard Wintersberger*

Institute of Molecular Biology, University of Vienna, A-1030 Vienna, Austria

Received 20 May 1999/Accepted 9 August 1999

Although polyomavirus large T antigen readily transactivates S-phase-specific enzymes in serum-starved Swiss 3T3 mouse fibroblasts, it is incapable by itself to efficiently drive such cells into S phase. We describe here that this inability correlates with a weak proficiency of the viral protein to induce the synthesis of cyclin A and cyclin E and to stimulate the respective cyclin/cdk activities. Polyomavirus small T antigen, which together with the large T protein supports S-phase induction, strongly contributes to the synthesis of cyclin A. In addition, small T antigen causes a dramatic induction of cyclin A- and, together with large T antigen, of cyclin E-specific protein kinase activity. This latter function of polyomavirus small T antigen correlates with its competence to provoke the elimination of the kinase inhibitor p27Kip1. An interaction of the small T antigen with the protein phosphatase 2A is essential for this activity. Hence, the ability to drive quiescent Swiss 3T3 cells into S phase results from the capacity of large T antigen to transactivate DNA synthesis enzymes by its interaction with retinoblastoma-type proteins and from the potential of the large and the small T antigens together to stimulate cyclin A synthesis and cyclin A- and cyclin E-dependent protein kinase activity.

* Corresponding author. Mailing address: Institut für Molekularbiologie, Universität Wien, Dr. Bohrgasse 9, A-1030 Vienna, Austria. Phone: 43-1-4277-61704. Fax: 43-1-4277-61705. E-mail: Wi{at}Mol.Univie.Ac.At.

Journal of Virology, November 1999, p. 9266-9273, Vol. 73, No. 11
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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