Date of Award
Spring 5-4-2022
Degree Type
Thesis
Degree Name
Master of Science (MS)
Department
Chemistry
First Advisor
Jun Yin
Abstract
Cbl-b is a representative member of Ring E3 that regulates cytotoxicity of the natural killer (NK) cells. Cbl-b also ubiquitinates TAM family of RTKs including Tyro3, Axl and Mer on the surface of NK cells to unleash their killing instinct against cancer cells. I focused on using phage display to engineer the Ring domain of Cbl-b so it can function as an xE3 to exclusively transfer an engineered UB (xUB) through an engineered xE1-xE2 cascade to its substrate proteins. The development of an orthogonal UB transfer (OUT) cascade of Cbl-b will enable us to profile its direct ubiquitination targets. Additionally, I used in-vitro ubiquitination to get the inhibition of sulfono-γ-AA peptide, a new class of peptidomimetic foldamer, to mimic the α-1 helix of E2 and thereby inhibiting E1/E2 protein-protein interaction so as to disrupt the ubiquitination signaling cascade.
DOI
https://doi.org/10.57709/29018432
Recommended Citation
Jeong, In, "Engineering an Orthogonal Ubiquitin Transfer (OUT) Cascade for Cbl-b, an E3 Ubiquitin Ligase Regulating Innate Immunity against Cancer Cells and Inhibition of the ubiquitin-proteasome system by peptidomimetic foldamer mimicking E2 N-terminal-helix." Thesis, Georgia State University, 2022.
doi: https://doi.org/10.57709/29018432
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