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Science. 1999 Jan 22;283(5401):543-6.

Prevention of constitutive TNF receptor 1 signaling by silencer of death domains.

Author information

  • 1Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA.

Erratum in

  • Science 1999 Mar 19;283(5409):1852.

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.

PMID:
9915703
[PubMed - indexed for MEDLINE]
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