The adenovirus (Ad) E1A oncoprotein can function as a transcriptional activator, a transcriptional repressor, a transforming protein, and some serotypes can function as tumorigenic proteins. These E1A functions are encoded by distinct subdomains of the protein many of which interact with specific cellular proteins including transcription factors. E1A interacts with cellular transcription factors Rb and p300 to deregulate cell growth. The E1A of Ad12 transformed cells represses expression of the major histocompatibility class I (MHCI) genes and this effect may allow virally infected cells to escape immune surveillance. In cells transformed by Ad12 E1A the promoter of the MHC H2K(b) gene shows decreased association with the activator NFkB at an R1 site and increased binding of the repressor COUP-TFII at a R2 site. Elucidation of these E1A effects on NFkB and COUP are the subject of the proposal. Also the ability of E1A to activate transcription will be studied by inhibition of E1A association with the hTAF135 by antibodies or introduced mutations. In addition NMR studies will be used to provide structural information.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Experimental Virology Study Section (EVR)
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Daschner, Phillip J
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University of Pennsylvania
Schools of Dentistry
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