Prevention of Constitutive TNF Receptor 1 Signaling by Silencer of Death Domains

See allHide authors and affiliations

Science  22 Jan 1999:
Vol. 283, Issue 5401, pp. 543-546
DOI: 10.1126/science.283.5401.543

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

This article has a correction. Please see:


Tumor necrosis factor receptor type 1 (TNF-R1) contains a cytoplasmic death domain that is required for the signaling of TNF activities such as apoptosis and nuclear factor kappa B (NF-κB) activation. Normally, these signals are generated only after TNF-induced receptor aggregation. However, TNF-R1 self-associates and signals independently of ligand when overexpressed. This apparent paradox may be explained by silencer of death domains (SODD), a widely expressed ∼60-kilodalton protein that was found to be associated with the death domain of TNF-R1. TNF treatment released SODD from TNF-R1, permitting the recruitment of proteins such as TRADD and TRAF2 to the active TNF-R1 signaling complex. SODD also interacted with death receptor–3 (DR3), another member of the TNF receptor superfamily. Thus, SODD association may be representative of a general mechanism for preventing spontaneous signaling by death domain–containing receptors.

  • * To whom correspondence should be addressed. E-mail: goeddel{at}

View Full Text