Hunter O'Reilly's 1997 DNA Tumour Virus Meeting Abstract

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This scientific abstract is from the 1997 DNA Tumour Virus Meeting held in Cambridge, England at Churchill College. Hunter O'Reilly gave a talk at this meeting showing and describing data and models related to this abstract.

REGULATION OF THE SV40 LATE PROMOTER BY NUCLEAR RECEPTORS AND SV40 LARGE T-ANTIGEN. Hunter O’Reilly, Fengrong Zuo, Stephen D. Johnston, and Janet E. Mertz. McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, WI 53706, USA.

In the absence of viral DNA replication, members of the steroid/thyroid hormone receptor superfamily [e.g., thyroid receptor alpha 1(TRalpha1)/retinoid X receptor alpha (RXRalpha) heterodimer, estrogen-related receptor alpha 1 (ERRalpha1)] repress transcription from the SV40 major late promoter (MLP) by binding directly over and/or 55 bp downstream of the site of initiation (Wiley et al. Genes Dev. 7:2206, 1993; Zuo and Mertz, P.N.A.S. 92:8586, 1995; Zuo and Mertz, J. Virol. 71:427, 1997). T-antigen derepresses the SV40-MLP in part via its roles in DNA replication leading to titration of these receptors. T-antigen also derepresses transcription of the SV40 late promoter in the absence of viral DNA replication. We have been interested in understanding the mechanisms of repression of the SV40-MLP by nuclear receptors and derepression by T-antigen. We have found the following: (i) The replication-independent component of derepression of the SV40-MLP by T antigen occurs in part via the +1 nuclear receptor-binding site. (ii) The co-repressor protein SMRT binds ERRalpha1 as well as TRalpha1. (iii) Amino acid residues 1-249 of T-antigen, containing the transactivation domains, also binds SMRT. (iv) A double amino acid substitution mutant of T antigen (K173A,K174A) is defective in both binding SMRT and in transactivation in a cell-free transcription system. Thus, we speculate that T-antigen’s titration of SMRT may lead to derepression/transactivation of the SV40-MLP and many cellular genes also regulated by nuclear receptors.

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