title: Analysis of human tumour necrosis factor receptor 1 dominant-negative mutants reveals a major region controlling cell surface expression.
abstract: Tumour necrosis factor receptor 1 (TNFR1) plays a critical role in host defence and inflammation. We have identified a membrane proximal region (aa 218-324) of TNFR1 that restricts surface expression. This was prompted by comparing the dominant-negative properties of a C-terminal truncation of TNFR1 with a point mutant that prevents signalling. C-terminal truncation (aa 218-426) generates a better dominant-negative TNFR1 mutant than inactivation of the death domain by point mutation. The increased dominant-negative activity correlates with increased cell surface expression. The membrane proximal region is the most important region of the receptor for restricting expression.
authors.affiliation: Infection and Immunity, University of Wales College of Medicine, Henry Wellcome Research Institute, Heath Park, Cardiff CF14 4XX, UK.
authors.forename: Ceri A
authors.initials: CA
authors.lastname: Fielding
authors.forename: Stefan
authors.initials: S
authors.lastname: Siebert
authors.forename: Martin
authors.initials: M
authors.lastname: Rowe
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
mesh_terms: D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005799:Genes, Dominant; D017930:Genes, Reporter; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D017354:Point Mutation; D017434:Protein Structure, Tertiary; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics* / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D014162:Transfection
chemical_list: D015703:Antigens, CD; D008164:Luminescent Proteins; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D049452:Green Fluorescent Proteins; D008156:Luciferases