Abstract
It is well established that the expression of simian virus 40 (SV40) early gene products causes oncogenic transformation of rodent cells. An important aspect of this process is the inactivation of the p53 and retinoblastoma (pRb) tumour suppressor proteins through interaction with the SV40 large tumour antigen (LT). In addition, the SV40 small tumour antigen (ST) may enhance LT induced transformation. Here we show that LT induces apoptotic cell death in rat embryo fibroblast (REF) cells and that ST functions to inhibit this effect by a mechanism which is different from other known anti-apoptotic proteins. Mutational analysis of LT indicates that mutants defective in the pRb-binding domain are unable to induce apoptosis whereas LT mutants defective in the p53-binding domain are still competent to induce apoptosis. Thus, interaction between LT and one or more pRb family members must occur for induction of apoptosis and that binding of p53 by LT is insufficient to inhibit LT induced apoptosis in REFs. The data presented herein suggest that the anti-apoptotic function of ST may explain, at least in part, how ST contributes to SV40 early region induced transformation of REF cells.
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Acknowledgements
We thank Dr M Reed (Stonybrook) for the p53ct expression plasmid, Dr D Simmons (Delaware) for the DE402 base construct, Dr L Sompayrac (Boulder) for the base constructs for mutants LE107 and aa147n. We also thank John Zhang for assistance with plasmid construction. This work was supported by grants from the Health Research Council of New Zealand, the Cancer Society of New Zealand and the Otago University Faculty Funds to A Braithwaite, and the Cancer Council of New South Wales to R Reddel.
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Kolzau, T., Hansen, R., Zahra, D. et al. Inhibition of SV40 large T antigen induced apoptosis by small T antigen. Oncogene 18, 5598–5603 (1999). https://doi.org/10.1038/sj.onc.1202942
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DOI: https://doi.org/10.1038/sj.onc.1202942
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