JC virus T'135, T'136 and T'165 proteins interact with cellular p107 and p130 in vivo and influence viral transformation potential

• Published in: Journal of neurovirology 2006-12, Vol.12 (6), p.428-442
• Main Authors: BOLLAG, Brigitte, KILPATRICK, Lisa H, TYAGARAJAN, Shiva K, TEVETHIA, Mary J, FRISQUE, Richard J
• Format: Article
• Language: English
• Subjects: Alternative Splicing; Animals; Antigens, Polyomavirus Transforming - metabolism; Antigens, Viral, Tumor - metabolism; Biological and medical sciences; Blotting, Western; Cell Line; Cell Transformation, Viral - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Human viral diseases; Infectious diseases; JC Virus - genetics; JC Virus - physiology; Medical sciences; Neurology; Rats; Retinoblastoma-Like Protein p107 - metabolism; Retinoblastoma-Like Protein p130 - metabolism; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Viral diseases of the nervous system; Viral Proteins - metabolism
• ISSN: 1355-0284; 1538-2443

The JC virus (JCV) regulatory proteins, large T antigen, small t antigen, T'135, T'136, and T'165, are encoded by five transcripts alternatively spliced from the viral early precursor mRNA. T antigen and the T' proteins share N-terminal amino acid sequences that include the L x CxE and J domains, motifs in SV40 T antigen known to mediate binding to the retinoblastoma (Rb) proteins and Hsc70, respectively. In this study, G418-resistant cell lines were created that express wild-type or mutant JCV T antigen and T' proteins individually or in combination. These cell lines were used to evaluate the ability of each viral protein to bind p107 and p130 in vivo, and to influence cellular growth characteristics. Differences were observed in the abilities of individual T' proteins to bind p107 and p130 and to alter their phosphorylation status. The T' proteins were also found to localize to the cell's nucleus and to be phosphorylated in a cell cycle-dependent manner. JCV T antigen and T' proteins expressed from a cytomegalovirus promoter failed to induce dense focus formation in Rat2 cells, but they did cooperate with a mutant Ras protein to overcome cellular senescence and immortalize rat embryo fibroblasts. These data indicate that, despite their sequence similarities, JCV early proteins exhibit unique activities that, in combination, effect the inactivation of cell cycle regulators, a requirement for polyomavirus-induced transformation.