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Analysis of human tumour necrosis factor receptor 1 dominant‐negative mutants reveals a major region controlling cell surface expression
Author(s) -
Fielding Ceri A,
Siebert Stefan,
Rowe Martin,
Brennan Paul
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.06.035
Subject(s) - mutant , tumor necrosis factor receptor 1 , dominant negative , receptor , point mutation , microbiology and biotechnology , tumor necrosis factor alpha , mutation , death domain , cell surface receptor , biology , necrosis , cell , programmed cell death , cell membrane , truncation (statistics) , inflammation , tumor necrosis factor receptor , apoptosis , genetics , gene , immunology , statistics , mathematics
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.