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Functional And Structural Mimicry Of A-Kinase Anchoring Proteins By Human Adenovirus E1a, Cason R. King
Functional And Structural Mimicry Of A-Kinase Anchoring Proteins By Human Adenovirus E1a, Cason R. King
Electronic Thesis and Dissertation Repository
As an obligate intracellular parasite, human adenovirus (HAdV) must utilize host factors for survival and replication. Early during infection, its multifunctional E1A protein interacts with an impressive range of cellular target proteins to exert control over the cellular environment. Through these virus-host interactions, E1A massively reprograms both viral and cellular transcription to activate the other HAdV genes, downregulate the host’s immune response, and induce the cell cycle. Consequently, E1A converts the infected cell into a compliant state more amenable for HAdV replication, resulting from its numerous protein-protein interactions. I sought to examine E1A’s interaction with cellular protein kinase A (PKA), …
Investigating Adenovirus E1a As An Rna Polymerase Ii C-Terminal Domain Mimic And Its Role In Transcription Activation, Kristianne Jc Galpin
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) …
The Interaction Of The Human Adenovirus E1a Protein With The Human Dref Transcription Factor, Kris M. James
The Interaction Of The Human Adenovirus E1a Protein With The Human Dref Transcription Factor, Kris M. James
Electronic Thesis and Dissertation Repository
The human adenovirus (HAdV) E1A protein is the first protein produced post-HAdV infection, and serves two main functions. The first is to modulate host and viral transcription. The second is to induce host cell cycle progression to S phase, to promote an optimal environment for viral replication. E1A performs its functions by binding and manipulating over 50 cellular factors. Interestingly, I found that E1A is capable of interacting with the poorly characterized human DNA replication-related element-binding factor (hDREF). hDREF is a transcription factor associated with the expression of several genes related to the cell cycle. I hypothesized that the interaction …
Human Adenovirus E1a Binds And Retasks Cellular Hbre1, Blocking Interferon Signalling And Activating Virus Early Gene Transcription, Gregory J. Fonseca
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 …