title: Mutation of the extracellular domain of tumour necrosis factor receptor 1 causes reduced NF-kappaB activation due to decreased surface expression.
abstract: Tumour necrosis factor receptor-associated periodic syndrome (TRAPS) results from point mutations in the extracellular domain of TNF receptor 1 (TNFRSF1A), but the effects of the mutations are controversial. This study shows that reduced NF-kappaB signalling is a feature of four TRAPS mutations. Reduced signalling correlates with reduced surface expression, measured by flow cytometry and microscopy. This suggests that correct formation of the extracellular domain of TNFRSF1A is important for localisation and receptor function. Importantly, our data provides a mechanism for the reduced TNFRSF1 signalling observed in a patient cell line.
authors.affiliation: Department of Medical Biochemistry and Immunology, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XX, United Kingdom.
authors.forename: Stefan
authors.initials: S
authors.lastname: Siebert
authors.forename: Ceri A
authors.initials: CA
authors.lastname: Fielding
authors.forename: Bryan D
authors.initials: BD
authors.lastname: Williams
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013577:Syndrome
chemical_list: D016328:NF-kappa B; D047888:Receptors, Tumor Necrosis Factor, Type I