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Characterizing The Interaction Between Human Adenovirus E1a And The Transcriptional Repressor Bs69, Ali Zhang

Electronic Thesis and Dissertation Repository

Protein products of the Early Region 1A (E1A) gene in human adenovirus 5 (HAdV-5) are the first viral proteins expressed upon adenovirus infection. E1A disrupts many cellular physiological events by binding to and regulating an impressive number of host factors. Of particular interest is BS69, a repressor of E1A transactivation. Due to the strong interaction observed between E1A and BS69, I hypothesize that these two proteins function together to disrupt gene expression within an infected cell.

Using in silico modelling and a series of yeast two-hybrid assays, I determined that residues 112-119 of HAdV-5 E1A is the minimal interacting region …

Investigating Adenovirus E1a As An Rna Polymerase Ii C-Terminal Domain Mimic And Its Role In Transcription Activation, Kristianne Jc Galpin

Electronic Thesis and Dissertation Repository

Viruses rely on host cell machinery, often mimicking cellular components, in order to circumvent host cell defenses and hijack cellular processes. DNA viruses, such as human Adenovirus (hAdV), rely on RNA Polymerase II (RNAPII) to transcribe viral genes. RNAPII has a C-terminal domain (CTD), made up of highly conserved heptad repeats of tyrosine-serine-proline-threonine-serine-proline-serine (YSPTSPS). Post-translational modifications of residues within the CTD, including phosphorylation, coordinates the transcription cycle. Several viruses, including Human Immunodeficiency Virus (HIV), Human Cytomegalovirus (hCMV), Epstein-Bar Virus (EBV) and Herpes Simplex Virus (HSV), modify the phosphorylation state of the RNAPII CTD by hijacking cellular cyclin dependent kinases (CDKs) …

Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca

Electronic Thesis and Dissertation Repository

Upon infection, human adenovirus (HAdV) must block interferon signaling and activate the expression of its early genes to reprogram the cellular environment to support virus replication. During the initial phase of infection, these processes are orchestrated by the first HAdV gene expressed during infection, early region 1A (E1A). E1A binds and appropriates components of the cellular transcriptional machinery to modulate cellular gene transcription and activate viral early genes transcription. We have identified hBre1/RNF20 as a novel target of E1A. hBre1 is an E3 ubiquitin ligase which acts with the Ube2b E2 conjugase and accessory factors RNF40 and WAC1 to monoubiquitinate …