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This scientific abstract describes data and models that Hunter Cole presented at the Genetics Colloquium at the University of Wisconsin-Madison on June 11, 1997.

Regulation of the SV40 Major Late Promoter by Hormone Receptors and Co-repressor Proteins

Presented by Hunter Cole, Genetics Graduate Student
(Janet E. Mertz, Major Professor)
3:30 PM, Wednesday, June 11, 1997
Auditorium, Genetics/Biotech Building

Abstract:

Hormonal changes in the body can effect the life cycle of many viruses. Until recently it was unknown whether the hormonal changes affect the regulation of viral genes directly through hormone receptors binding viral promoters or indirectly through a signal transduction cascade. Our lab uses simian virus 40 (SV40) as a model system to study the regulation of viral genes by nuclear hormone receptors.


SV40 is a primate DNA tumor virus whose genome is 5,243 bp in size. Infection primarily occurs in monkey kidney cells. The early genes, expressed early in the lytic cycle, include large T antigen and small t antigen. The late genes, expressed late in the lytic cycle under the control of the SV40 major late promoter (MLP), include virion proteins.


Our lab has shown many host proteins that are members of the steroid/thyroid hormone receptor superfamily regulate transcription of the SV40-MLP by binding directly over and/or 55 bp downstream of the site of initiation. We are studying the regulation of the SV40-MLP by the following steroid/thyroid hormone receptors: the thyroid receptor (TR)/retinoid X receptor heterodimer (RXR), estrogen-related receptor (ERR), and the liver X receptor (LXR)/retinoid X receptor (RXR) heterodimer.


SMRT, a co-repressor protein, represses transcription of at least
some TR regulated genes through binding unliganded TR. Our lab has found that SMRT also binds ERR and SV40 large T antigen. We are continuing to look at the effects of these protein interactions with SMRT on transcription of the SV40-MLP. In the future, we plan to look at the effects these hormone receptors and their ligands have on SV40 virus production.

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