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The poxvirus ubiquitin ligase p28 manipulates the ubiquitin proteasome system

  • Author / Creator
    Mottet, Kelly
  • The significance of poxvirus manipulation of the host ubiquitin proteasome system has become increasingly apparent. Ubiquitin is post-translationally added to target proteins by a highly conserved enzymatic cascade, typically resulting in protein degradation via the 26S proteasome. The highly conserved poxvirus protein, p28, is a functional ubiquitin ligase and a critical virulence factor. Here, we investigate the relationship between p28 and ubiquitination. We observed that the KilA-N DNA binding domain in p28 targeted p28 to viral factories, where p28 co-localized with conjugated ubiquitin. Furthermore, we determined that p28 is highly regulated by ubiquitination and proteasomal degradation. Disruption of p28 ubiquitin ligase activity revealed that p28 is regulated through auto-ubiquitination and ubiquitination by an additional unknown ubiquitin ligase. Moreover, we observed Lysine-48 ubiquitin linkages, Lysine-63 ubiquitin linkages and a proteasomal subunit co-localizing with p28 at the viral factory, suggesting an intricate relationship between p28 and proteasomal degradation.

  • Subjects / Keywords
  • Graduation date
    2010-11
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3BT1M
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Department of Medical Microbiology and Immunology
  • Supervisor / co-supervisor and their department(s)
    • Barry, Michele (Medical Microbiology and Immunology)
  • Examining committee members and their departments
    • Pukatzki, Stefan (Medical Microbiology and Immunology)
    • Smiley, James (Medical Microbiology and Immunology)
    • Berthiaume, Luc (Cell Biology)