Analysis of human tumour necrosis factor receptor 1 dominant-negative mutants reveals a major region controlling cell surface expression

Tumour necrosis factor receptor I (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. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.