Investigating the function of TRAF1 in NF-κB activation

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dc.contributor.advisorAbdul-Sater, Ali
dc.contributor.authorTang, Yitian
dc.date.accessioned2024-03-18T18:20:50Z
dc.date.available2024-03-18T18:20:50Z
dc.date.issued2024-03-16
dc.date.updated2024-03-16T10:37:52Z
dc.degree.disciplineKinesiology & Health Science
dc.degree.levelMaster's
dc.degree.nameMSc - Master of Science
dc.description.abstractTumour necrosis factor receptor-associated factor (TRAF) proteins play an important role in mediating the activation of NF-κB. Dysregulation of NF-κB may be one of the potential causes of chronic inflammatory diseases. One member of the TRAF family, TRAF1, has been shown to increase the risk of rheumatoid arthritis (RA). However, TRAF1 plays opposing roles in the activation of NF-κB downstream of the tumour necrosis factor receptors (TNFR) and toll-like receptors (TLR) signalling pathways. In the TNFR pathway, TRAF1 recruits c-IAP2 to promote NF-κB activation and cell proliferation. In contrast, in TLR pathways, TRAF1 negatively regulates NF-κB by sequestering the linear ubiquitin assembly complex (LUBAC). Because of the complex role of TRAF1 in NF-κB activation, it is important to isolate and study the role of TRAF1 in each of these pathways. To better understand TRAF1 and its role in NF-κB activation, our laboratory has identified the same interaction site between TRAF1 and c-IAP2 and created a mutant TRAF1V203A that significantly reduces the interaction with c-IAP2. This study creates a working functional assay to test the effect of these mutants on NF-κB activation. We have generated TRAF1V203A knock-in monocyte THP-1 cells and demonstrated how this mutant alters signalling downstream of TLR and TNFR in monocytes. This study also shows that the production of pro-inflammatory cytokines is reduced in TRAF1V203A mutant monocytes. This study helps us to isolate effects on NF-κB activation and provides an excellent model to study the role of TRAF1 in vivo.
dc.identifier.urihttps://hdl.handle.net/10315/41975
dc.languageen
dc.rightsAuthor owns copyright, except where explicitly noted. Please contact the author directly with licensing requests.
dc.subjectImmunology
dc.subjectMolecular biology
dc.subject.keywordsInflammation
dc.subject.keywordsTRAF1
dc.subject.keywordsCIAP2
dc.subject.keywordsNF-κB
dc.subject.keywordsRheumatoid arthritis
dc.titleInvestigating the function of TRAF1 in NF-κB activation
dc.typeElectronic Thesis or Dissertation

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