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

• DOI: 10.1126/science.283.5401.543
• Publication Date: 2002-07-27T09:48:21Z
• Authors: Yingping Jiang; John D. Woronicz; Wei Liu; David V. Goeddel
• Keywords: Silencer

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 kappa B (NF-κB) activation. Normally, these signals are generated only after TNF-induced aggregation. However, TNF-R1 self-associates independently ligand when overexpressed. This apparent paradox may be explained by silencer domains (SODD), widely expressed ∼60-kilodalton protein was found to associated with TNF-R1. treatment released SODD from TNF-R1, permitting recruitment proteins TRADD TRAF2 active complex. also interacted receptor–3 (DR3), another member superfamily. Thus, association representative general mechanism preventing spontaneous domain–containing receptors.