Research Article: Simian virus 40 large T antigen-mediated transactivation of the cyclin A promoter is independent of p53 and TBP binding functions

Abstract

Abstract Simian virus 40 is a small DNA tumor virus capable of transforming cells in culture and causing tumors in animal models. The viral protein large T antigen specifically binds the tumor suppressors p53 and hypophosphorylated retinoblastoma protein (pRb) to prevent G1 arrest. T antigen also transactivates the cyclin-A promoter. This activity is independent of pRb binding, yet dependent upon the J-domain Hsp70-binding region. T antigen also binds transcription factors, including TATA box binding protein (TBP). Thus, we assessed whether cyclin A promoter activation relied on this activity and/or the ability to complex with p53. Using a luciferase reporter assay, we show that T antigen mutant proteins defective in TBP and p53 binding are able to transactivate the cyclin A promoter to wild type levels. These data indicate that T antigen mediated transactivation of the cyclin A promoter uses a p53 and TBP-binding-independent mechanism, yet relies on hsp70 binding to the N-terminal, J-domain. This suggest...