The ECS Type E3 Ubiquitin Ligase TULP4 Targets MAL to Inhibit the TLR4-Mediated NFκB Innate Immune Pathway

• Main Author: Xu, Amanda Shelley Fox
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-2016
• Subjects: Biochemistry; Microbiology; Molecular biology
• ISBN: 1369311168; 9781369311167

It is our ability to respond to pathogens, and often more importantly, revert back to homeostasis which allows us to survive. Tubby-like protein 4 (TULP4) is a novel putative immunoregulatory protein, which may be pertinent for this reversal process. Many bacterially induced mortalities are not due solely to an overwhelming pathogenic load, but to sepsis. Sepsis caused by gram negative bacteria is often a result of the host’s response to lipopolysaccharide (LPS). TULP4 may be significant for the inhibition of the host’s immune response to the LPS stimulated Toll-like receptor 4 (TLR4) signaling cascade. This dissertation explores both where and mechanistically how TULP4 implements this regulation of the innate inflammatory response. Chapter 1 introduces what is currently known about TULP4, TLR innate immune signaling and the ubiquitin proteasome system that is known to regulate it. Chapter 2 defines TULP4 as an innate immune inhibitor and explores where within the TLR4-mediated NF?B signaling cascade TULP4 functions whereas, Chapter 3 examines the ubiquitin ligase mechanism and target of TULP4’s inhibition. Finally, Chapter 4 discusses future experiments which will better clarify TULP4’s inhibitory role and associated potential therapeutic strategies for treatment of immune related conditions.