Publication Date:
1999-01-23
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Jiang, Y -- Woronicz, J D -- Liu, W -- Goeddel, D V -- New York, N.Y. -- Science. 1999 Jan 22;283(5401):543-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Tularik, Two Corporate Drive, South San Francisco, CA 94080, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/9915703" target="_blank"〉PubMed〈/a〉
Keywords:
*Adaptor Proteins, Signal Transducing
;
Amino Acid Sequence
;
Antigens, CD/chemistry/genetics/*metabolism
;
Apoptosis
;
Carrier Proteins/chemistry/genetics/*metabolism
;
Cell Line
;
Fas-Associated Death Domain Protein
;
Humans
;
Jurkat Cells
;
Molecular Sequence Data
;
Mutation
;
NF-kappa B/metabolism
;
Protein Binding
;
Proteins/metabolism
;
Receptor Aggregation
;
Receptor-Interacting Protein Serine-Threonine Kinases
;
Receptors, Tumor Necrosis Factor/chemistry/genetics/*metabolism
;
Receptors, Tumor Necrosis Factor, Member 25
;
Receptors, Tumor Necrosis Factor, Type I
;
Recombinant Fusion Proteins/metabolism
;
*Signal Transduction
;
TNF Receptor-Associated Factor 1
;
TNF Receptor-Associated Factor 2
;
Transfection
;
Tumor Necrosis Factor-alpha/pharmacology
;
U937 Cells
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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