Lauren Fulham, University of Manitoba

Lauren Fulham (Department of Microbiology, University of Manitoba, Canada), Nathaniel Casiano (Department of Microbiology, University of Manitoba, Canada), Jordan Rempel (Department of Microbiology, University of Manitoba, Canada), Rafe Helwer (Department of Microbiology, University of Manitoba, Canada), Peter Pelka (Department of Microbiology, University of Manitoba, Canada)

Suppressing & Conquering

Human Ubiquitin Protein Ligase E3 Component N-recognin 4 (UBR4) is best known for its role in protein degradation via the ubiquitin proteasome. However, our lab amongst others, have identified UBR4 as a cellular hub protein. Specifically, our lab is investigating how human Adenovirus C5 (HAdV-C5) utilizes UBR4 during infections. HAdV expresses Early Region 1A and 1B (E1A and E1B) proteins that are required for a productive infection and deregulate host cellular interaction networks via targeting of hub proteins. Through these interactions, E1A and E1B proteins disrupt various aspects of the human cell. We have identified UBR4 as a novel interaction partner of E1A and E1B proteins and aim to elucidate the consequences of these interactions. Recently, we have discovered that under conditions of UBR4 knockdown, levels of interferon-stimulated genes (ISGs) are elevated in infected cells. This difference is seen with interferon treatment early in infection suggesting that UBR4 may function in the activation of ISGs. Moreover, when UBR4 is knocked down, histone H3 occupancy increases at ISG promoters in uninfected cells, but decreases in infected cells. Consequently, we found that viral growth and viral genome copies decrease when UBR4 is knocked down in the cell. Our results identify UBR4 as a previously unknown player in chromatin organization and transcriptional regulation of ISGs in response to HAdV infection. Moreover, our studies provide insight in how HAdV disrupts UBR4 during viral infection in addition to unravelling the role of this protein in the cell.