Cell
Volume 74, Issue 5, 10 September 1993, Pages 845-853
Journal home page for Cell

Article
A novel domain within the 55 kd TNF receptor signals cell death

https://doi.org/10.1016/0092-8674(93)90464-2Get rights and content

Abstract

Deletion mutagenesis of the intracellular region of the 55 kd TNF receptor (TNF-R1) identified an ∼80 amino acid domain near the C-terminus responsible for signaling cytotoxicity. This domain shows weak homology with the intracellular domain of Fas antigen, a transmembrane polypeptide that can also initiate a signal for cytotoxicity. Alanine-scanning mutagenesis of TNF-R1 confirmed that many of the amino acids conserved with Fas antigen are critical for the cytotoxic signal. This region of TNF-R1-Fas homology is therefore likely to define a novel domain (death domain) that signals programed cell death. Mutations within the death domain of TNF-R1 also disrupted its ability to signal anti-viral activity and nitric oxide (NO) synthase induction. In addition, large deletions in the membrane-proximal half of the intracellular domain did not block signaling of cytotoxicity or anti-viral activity but did block induction of NO synthase.

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