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- Title
Prevention of constitutive TNF receptor 1 signaling by silencer of death domains.
- Authors
Jiang, Y; Woronicz, J D; Liu, W; Goeddel, D V
- Abstract
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-kappaB) 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 approximately 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.
- Publication
Science (New York, N.Y.), 1999, Vol 283, Issue 5401, p543
- ISSN
0036-8075
- Publication type
Journal Article
- DOI
10.1126/science.283.5401.543