Type

Text

Type

Thesis

Advisor

Hearing, Patrick | Krug, Laurie T

Date

2017-12-01

Keywords

Microbiology | Cytology | Biochemistry

Department

Department of Biochemistry and Cell Biology

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/78219

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Viruses have evolved many tactics to ensure robust infection and proliferation. Similarly, human adenovirus employs such techniques that include direct sequestration of cellular antiviral proteins and modulation of host cellular pathways. The viral protein E4ORF3 plays a critical role in carrying out these functions during infection. This protein is unique in its ability to form a nuclear scaffold during infection, which then serves as an interface for cellular protein binding. It has been previously shown that E4ORF3 is responsible for the reorganization of critical antiviral cellular proteins including MRN and TRIM family proteins. Also, it has been established that the elaborate network formed by E4ORF3 is due to crosslinking in its C-terminal tail. However, not much is known about how vital a role the residues in this region play regarding both oligomerization and the ability to reorganize different cellular proteins. Mutational analysis revealed I104A as a new C-terminal mutant incapable of forming a normal track network, as well as suggesting critical binding motifs on E4ORF3 for the sequestration of PML and TIF1g. To study further E4ORF3's modulation of the host sumoylation pathway, a cell line was established to perform a proteomics screen of E4ORF3-induced SUMO1 modifications on cellular proteins to deduce novel cellular proteins targeted during infection. | 40 pages

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