STANDARD_NAME	BIOCARTA_SODD_PATHWAY
SYSTEMATIC_NAME	M2699
COLLECTION	C2:CP:BIOCARTA
MSIGDB_URL	https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BIOCARTA_SODD_PATHWAY
NAMESPACE	Human_RefSeq
DESCRIPTION_BRIEF	SODD/TNFR1 Signaling Pathway
DESCRIPTION_FULL	The tumor necrosis factor (TNF) receptor superfamily contains several members with homologous cytoplasmic domains known as death domains (DD). The intracellular DD are important in initiating apoptosis and other signaling pathways following ligand binding by the receptors.1 In the absence of ligand, DD-containing receptors are maintained in an inactive state. TNF RI contains a cytoplasmic DD required for signaling pathways associated with apoptosis and NF-kB activation.2,3 Jiang et al.4 identified a widely expressed 60 kDa protein, named SODD (silencer of death domains), associated with the DD of TNF RI and DR3. Overexpression of SODD suppresses TNF-induced cell death and NF-kB activation demonstrating its role as a negative regulatory protein for these signaling pathways. TNF-induced receptor trimerization aggregates the DD of TNF RI and recruits the adapter protein TRADD.3,5 This in turn promotes the recruitment of the DD-containing cytoplasmic proteins FADD, TRAF2 and RIP to form an active TNF RI signaling complex (Figure 1A).6-9 In contrast, SODD acts as a silencer of TNF RI signaling and does not interact with TRADD, FADD, or RIP (Figure 1B).4 It is associated with the DD of TNF RI and maintains TNF RI in an inactive, monomeric state. TNF-induced aggregation of TNF RI promotes the disruption of the SODD-TNF RI complex. SODD does not interact with the DD of other TNF receptor superfamily members such as Fas, DR4, DR5, or TNF RII. SODD association with TNF RI may represent a general model for the prevention of spontaneous TNF signaling by other DD-containing receptors.
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CONTRIBUTOR	BioCarta
CONTRIBUTOR_ORG	BioCarta
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EXTERNAL_DETAILS_URL	https://data.broadinstitute.org/gsea-msigdb/msigdb/biocarta/human/h_soddPathway.gif
SOURCE_MEMBERS	NM_000594,NM_001065,NM_001066,NM_001080124,NM_001080125,NM_001165,NM_001204878,NM_001228,NM_003789,NM_003804,NM_003824,NM_004874,NM_021138,NM_033355,NM_033356,NM_033358,NM_182962
GENE_SYMBOLS	TNF,TNFRSF1A,TNFRSF1B,CASP8,CASP8,BIRC3,BAG4,CASP8,TRADD,RIPK1,FADD,BAG4,TRAF2,CASP8,CASP8,CASP8,BIRC3
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