SV40 large T antigen targets multiple cellular pathways to elicit cellular transformation

Abstract

DNA tumor viruses such as simian virus 40 (SV40) express dominant acting oncoproteins that exert their effects by associating with key cellular targets and altering the signaling pathways they govern. Thus, tumor viruses have proved to be invaluable aids in identifying proteins that participate in tumorigenesis, and in understanding the molecular basis for the transformed phenotype. The roles played by the SV40-encoded 708 aminoacid large T antigen (T antigen), and 174 amino acid small T antigen (t antigen), in transformation have been examined extensively. These studies have firmly established that large T antigen's inhibition of the p53 and Rbfamily of tumor suppressors and small T antigen's action on the pp2A phosphatase, are important for SV40-induced transformation. It is not yet clear if the Rb, p53 and pp2A proteins are the only targets through which SV40 transforms cells, or whether additional targets await discovery. Finally, expression of SV40 oncoproteins in transgenic mice results in effects ranging from hyperplasia to invasive carcinoma accompanied by metastasis, depending on the tissue in which they are expressed. Thus, the consequences of SV40 action on these targets depend on the cell type being studied. The identification of additional cellular targets important for transformation, and understanding the molecular basis for the cell type-specific action of the viral T antigens are two important areas through which SV40 will continue to contribute to our understanding of cancer.

Oncogenic ras-driven cancer cell vesiculation leads to emission of double-stranded DNA capable of interacting with target cells

“…These cells are deficient for both Rb/TP53 activity (due to SV40LT expression [27]) and ASMase (due to targeted insertion of neomycin expressing cassette into the gene [28]), the changes affecting both known vesiculation pathways of exosomal and ectosomal biogenesis, respectively [24,26]. Analysis of this unique panel of cell lines revealed the emission of EVs containing oncogenic N-ras and SV40LT sequences, suggesting EV biogenesis may be independent of the two pathways (Fig.…”

Reprogramming of ovine adult fibroblasts to pluripotency via drug-inducible expression of defined factors

“…These observations suggest that SV40 large T plays an essential role in reprogramming sheep somatic cells. SV40 large T is an essential protein for SV40 DNA replication and disables the retinoblastoma and p53 tumor suppressor pathways [31][32][33][34]. It has been reported that knocking down p53 greatly increases reprogramming efficiency [35][36][37][38][39].…”

Adenoviral E1B55K oncoprotein sequesters candidate leukemia suppressor sequence-specific single-stranded DNA-binding protein 2 into aggresomes

“…Sequestration of tumor suppressor proteins by viral oncoproteins is a mechanism commonly employed by oncogenic viruses (Ahuja et al, 2005;O'Shea, 2005;Weitzman and Ornelles, 2005;Felsani et al, 2006). The adenoviral oncoproteins E1A and E1B55K cooperate to transform primary cells in culture (Endter and Dobner, 2004).…”