Cellular Transformation by Polyomavirus Oncoproteins

Polyomaviruses have contributed tremendously towards our understanding of molecular biology of the cell and especially in discovering cellular factors and pathways involved in cancer formation and progression. Polyomavirus encoded oncoproteins manipulate specific cellular molecular pathways to create cellular environment conducive for viral replication and persistence. In a non-productive infection, the alteration of such cellular pathways by polyomaviral oncoproteins leads to activation of certain "cancer hallmarks" and results into cell transformation. In one part of this study, I used polyomaviral oncoproteins as a molecular tool to understand and decode cellular pathways involved in cell transformation. In one part of this study, I used a well characterized oncoprotein of polyomavirus Simian Virus 40 (SV40), called the large tumor antigen (TAg), as a molecular and genetic tool to understand the role of RB/E2F pathway in oncogene mediated cell transformation. According to the current paradigm, activator E2Fs are considered essential for cell proliferation and oncogenic transformation. My results, contrary to the current paradigm, suggest that TAg activates an alternative molecular pathway to induce proliferation and transformation in the absence of activator E2Fs.\ud \ud In another project, I have studied oncoproteins encoded by a less studied polyomavirus, Lymphotropic Papovavirus (LPV). I have discovered previously unknown splice forms of LPV early region, and their comparative analysis with SV40 oncoproteins suggest distinct roles for the homologous proteins in cellular immortalization and transformation. Importantly, my research shows an essential role of LPV small tumor antigen (sT) in immortalization and transformation of primary murine embryonic fibroblasts