• Libraries
    • Log in to:
    View Item 
    •   MSpace Home
    • Faculty of Graduate Studies (Electronic Theses and Practica)
    • FGS - Electronic Theses and Practica
    • View Item
    •   MSpace Home
    • Faculty of Graduate Studies (Electronic Theses and Practica)
    • FGS - Electronic Theses and Practica
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Investigating the interaction of two human adenovirus 5 proteins: E1A and E4orf3 and the contribution of E1A C terminus on human adenovirus 5 replicative cycle

    Thumbnail
    View/Open
    Soriano_Andrea.pdf (3.071Mb)
    Date
    2018-08-01
    Author
    Soriano, Andrea
    Metadata
    Show full item record
    Abstract
    Human adenovirus is a useful model system to study cellular processes such as DNA replication, transcription, splicing and the initiation of malignant transformation by DNA tumour viruses. The HAdV5 early region 1A protein (E1A) is the first protein to be expressed upon viral infection. Here we report, for the first time, the viral early protein E4orf3 as a novel binding partner of the E1A protein. E4orf3 is a 15kDa protein that weaves through the nucleus of infected cells self-polymerizing into cable-like tracks. E4orf3 functions by forming multiple protein binding interfaces to capture and disrupt numerous cellular protein complexes including members of the DNA damage complex composed of Mre11, Nbs1 and Rad50 (MRN complex) and the oligomeric proteins Promyelocytic Leukemia (PML), amongst others. E4orf3 has also been found to block activation of p53 responsive genes via the formation of repressive heterochromatin at p53 target promoters. We found that E4orf3 binds directly to E1A via the N terminus of E1A. The presence of E4orf3 enhances E1A mediated transcriptional activity of viral genes thus driving their upregulation. In addition, we found that while the E4orf3 protein contributes to inactivation of p53, it is unlikely to be sufficient to block p53 mediated transcription. Instead, our results suggest that E1A and E4orf3 may be working together to achieve suppression of the p53 response pathway. The second project in this thesis focuses on the functions of the second exon-encoded region of E1A referred to as the C terminus of E1A. This region, is involved in a variety of processes including the regulation of viral and cellular gene expression, immortalization and transformation. Using various exon 2 deletion mutants we found that the C terminus of E1A makes important contributions to the viral life cycle in terms of kinetics of virus growth, activation of viral and cellular gene expression, efficiency of viral genome replication and deregulation of the cell cycle for the induction of S-phase.
    URI
    http://hdl.handle.net/1993/33463
    Collections
    • FGS - Electronic Theses and Practica [25525]

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV
     

     

    Browse

    All of MSpaceCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects

    My Account

    Login

    Statistics

    View Usage Statistics

    DSpace software copyright © 2002-2016  DuraSpace
    Contact Us | Send Feedback
    Theme by 
    Atmire NV