This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Manfredi, J J Articles by Prives, C Search for Related Content PubMed PubMed Citation Articles by Manfredi, J J Articles by Prives, C

Binding of p53 and p105-RB is not sufficient for oncogenic transformation by a hybrid polyomavirus-simian virus 40 large T antigen.

Department of Biological Sciences, Columbia University, New York, New York 10027.

ABSTRACT

To identify regions on the large T antigens of simian virus 40 (SV40) and polyomavirus which are involved in oncogenic transformation, we constructed plasmids encoding hybrid polyomavirus-SV40 large T antigens. The hybrid T antigens were expressed in G418 sulfate-resistant pools of rat F2408 cells, and extracts of such pools were immunoprecipitated with an antibody against p53. Two hybrid T antigens containing SV40 amino acids 337 to 708 bound to p53, whereas another hybrid T antigen containing SV40 amino acids 412 to 708 did not. This suggests that a binding domain on SV40 large T antigen for p53 is contained within amino acids 337 to 708, with amino acids 337 to 411 playing an important role. One of the two hybrids that bound to p53 was chosen for further study. This T antigen contained SV40 large T antigen amino acids 336 to 708 joined to polyomavirus large T antigen amino acids 1 to 521 (PyT1-521-SVT336-708). Immunoprecipitation with antibodies directed against the product of the retinoblastoma susceptibility gene, p105-RB, showed that this hybrid bound p105-RB as well as p53. Pools expressing the hybrid PyT1-521-SVT336-708 did not grow in soft agar, nor did they form foci on confluent monolayers of nontransformed F2408 cells. The hybrid T antigen was expressed at levels comparable to those seen in retrovirus-infected F2408 cells expressing only SV40 large T antigen, which do show a transformed phenotype. Thus, this level of expression was sufficient for transformation by SV40 large T antigen but not for the hybrid large T antigen. These data, combined with genetic studies from other laboratories, suggest that complex formation with p53 and p105-RB is necessary but not sufficient for the oncogenic potential of papovavirus large T antigens.

This article has been cited by other articles:

• Kasper, J. S., Kuwabara, H., Arai, T., Ali, S. H., DeCaprio, J. A. (2005). Simian Virus 40 Large T Antigen's Association with the CUL7 SCF Complex Contributes to Cellular Transformation. J. Virol. 79: 11685-11692 [Abstract] [Full Text]  
• MacIvor, D. M., Pham, C. T.N., Ley, T. J. (1999). The 5' Flanking Region of the Human Granzyme H Gene Directs Expression to T/Natural Killer Cell Progenitors and Lymphokine-Activated Killer Cells in Transgenic Mice. Blood 93: 963-973 [Abstract] [Full Text]  
• Gottifredi, V, Peschiaroli, A, Fimia, G., Maione, R (1999). p53-independent apoptosis induced by muscle differentiation stimuli in polyomavirus large T-expressing myoblasts. J. Cell Sci. 112: 2397-2407 [Abstract]