Translator Disclaimer
1 December 2016 Research Article: Simian virus 40 large T antigen-mediated transactivation of the cyclin A promoter is independent of p53 and TBP binding functions
Author Affiliations +
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 suggests that upregulation of cyclin A by T antigen could be initiated via the J-domain, in an ATPase-dependent process to disrupt transcriptional regulators, in a yet to be determined mechanism.

Copyright Beta Beta Beta Biological Society
Emily A. Girsch, Dillon McDevitt, Kyle Lord, Stacey Lehman, and Jane F. Cavender "Research Article: Simian virus 40 large T antigen-mediated transactivation of the cyclin A promoter is independent of p53 and TBP binding functions," BIOS 87(4), 138-145, (1 December 2016). https://doi.org/10.1893/BIOS-D-15-00007.1
Received: 17 July 2015; Accepted: 1 February 2016; Published: 1 December 2016
JOURNAL ARTICLE
8 PAGES


SHARE
ARTICLE IMPACT
RIGHTS & PERMISSIONS
Get copyright permission
Back to Top