Keywords
inflammation; NOD2; RIP2; XIAP; ALOX5; FLAP
Abstract
Inflammation is an essential immune response. However, dysregulated inflammation can result in chronic inflammatory diseases, like Crohn’s disease, Blau syndrome, and early-onset sarcoidosis. Receptor-interacting serine/threonine protein kinase 2 (RIP2) is a kinase that plays a critical role in nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1 and 2) signaling pathways, ultimately triggering NF-kB activation and the secretion of pro- inflammatory cytokines. Our laboratory discovered that RIP2 also promotes the activation of arachidonate 5-Lipoxygenase (ALOX5 or 5LO), an enzyme important for producing lipid mediators. Interaction of RIP2 with the X-linked inhibitor of apoptosis protein (XIAP) has been demonstrated to be crucial for NF-kB activation and cytokine production. The purpose of this project is to determine if and how RIP2:XIAP interactions influence ALOX5 activity. This project utilizes transient transfection, competitive inhibition, fractionation, co-immunoprecipitation, SDS- PAGE, and Western blotting to analyze how disrupting RIP2:XIAP interactions influences ALOX5-activating phosphorylation and ALOX5 association with FLAP (5-Lipoxygenase Activating Protein). This study also discusses the development of a fluorescenct imaging assay to capture ALOX5:FLAP interactions. Our results indicate that RIP2:XIAP interactions are dispensable for RIP2-mediated ALOX5 activation. Understanding the mechanisms by which RIP2 influences ALOX5 will be helpful in the design, development, and testing of drugs treating NOD2-associated inflammatory diseases.
Thesis Completion Year
2025
Thesis Completion Semester
Spring
Thesis Chair
Tigno-Aranjuez, Justine
College
College of Medicine
Department
Burnett School of Biomedical Sciences
Thesis Discipline
Biomedical Sciences
Language
English
Access Status
Campus Access
Length of Campus Access
3 years
STARS Citation
Murugesan, Vishanth, "Understanding the Role of Receptor-Interacting-Protein Kinase 2 and X-Linked Inhibitor of Apoptosis Interactions on 5-Lipoxygenase Activation" (2025). Honors Undergraduate Theses. 292.
https://stars.library.ucf.edu/hut2024/292
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