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    • Albert Einstein College of Medicine: Doctoral Dissertations
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    • Albert Einstein College of Medicine: Doctoral Dissertations
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    Modulation of cell signal transduction pathways by adenovirus E3 and an E3 -14.7K -interacting cell protein

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    Date
    2002
    Author
    Friedman, Joshua Michael
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    Abstract
    The pro-inflammatory cytokine, TNFalpha, is a molecule central to the immune response against various cellular stresses and pathogens such as Adenovirus (Ad). Several products of the Ad genome including E1B-19K, E3-10.4K, E3-14.5K, and E3-14.7K are able to prevent TNFalpha induced cytolysis. In order to understand the mechanism of E3-14.7K prevention of cytolysis induced by TNFalpha, we performed a yeast two-hybrid assay and isolated several 14.7K interacting proteins (FIPs). We have extensively studied one of these FIPs, FIP-3 (also reported as IKKgamma or NEMO) and have demonstrated that it plays an important role in the regulation of the NF-kappaB signal transduction pathway and induces apoptotic cell death after transfection. Furthermore, our studies have also shown that FIP-3/IKKgamma/NEMO is an important modulator of the transcription factor AP-1. FIP3/IKKgamma/NEMO interacts with AP-1 and when overexpressed, significantly induces AP-1 activity through c-Jun. The phosphorylation state of c-Jun is affected both by transient transfections of FIP-3/IKKgamma/NEMO as well as in FIP-3/IKKgamma/NEMO deficient Jurkat cells. Since we isolated FIP-3/IKKgamma/NEMO using an Ad E3 protein, we were interested in determining whether the E3 region could modulate NF-kappaB signaling during viral infection. As a result of these studies, we have shown that the E3 region of group C Ads can inhibit the activation of NF-kappaB by TNFalpha and IL-1. However, by using adenoviruses with selected deletions of individual E3 genes, we demonstrated that the effect of the Ad E3 region on NF-kappaB activity mapped to the E3 10.4/14.5K-protein complex. Through these studies we have demonstrated that Ad E3 products and the cellular proteins they interact with are important molecules on pathways that affect the host immune response.
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    https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3041820
    https://hdl.handle.net/20.500.12202/563
    Citation
    Source: Dissertation Abstracts International, Volume: 63-02, Section: B, page: 6270.;Advisors: Marshall S. Horwitz.
    *This is constructed from limited available data and may be imprecise.
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    • Albert Einstein College of Medicine: Doctoral Dissertations [1673]

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