Pathway Map Details
Apoptosis and survival_Apoptotic TNF-family pathways
Object list (links open in MetaCore):
NGFR (TNFRSF16), TRADD, TWEAK(TNFSF12), Bid = tBid, GITR (TNFRSF18), CD70(TNFSF7), Caspase-7, Caspase-9, RAIDD, Bcl-XL, DR4 (TNFRSF10A), TNF-alpha, LIGHT(TNFSF14), FADD, FasR (CD95), TRAF2, Caspase-10, FasL(TNFSF6), BAX, Bcl-2, RIPK1, tBid, TRAF3, NADE (NGFRAP1), DR6 (TNFRSF21), LTBR (TNFRSF3), XIAP, CD27BP, Caspase-8, Apo-2L(TNFSF10), Caspase-3, TNFSF18, TNF-R1, DR5 (TNFRSF10B), Smac/Diablo, NGF, CD27 (TNFRSF7), TNF-R2, Bid, DR3 (TNFRSF12), Caspase-2, c-IAP1
Apoptotic TNF-family pathways
Members of the tumour necrosis factor ligand family (TNFs) induce both apoptotic and anti-apoptotic pathways. TNFs transduce cellular responses through activation of different TNF-receptors (TNFRs) , , .
Different TNF/TNFRs may activate some pro-apoptotic proteins (e.g. members of the cysteine-aspartic acid protease (caspase) family) or inhibit some anti-apoptotic proteins (e.g. members of the Bcl-2 family). Thus, TNF/TNFRs exert influence on apoptosis via caspase cascade and via mitochondrial proteins .
Apoptotic signals from TNFR superfamily, member 1A ( TNF-R1 ) , TNFR superfamily, member 12 ( DR3 ) , TNFR superfamily, member 10a ( DR4 ) , TNFR superfamily, member 10b ( DR5 )  and, possibly, TNFR superfamily, member 21 ( DR6 )  are mediated by TNFRSF1A-associated via death domain ( TRADD ) and/or Fas (TNFRSF6)-associated via death domain ( FADD ). Receptor TNFR-interacting serine-threonine kinase 1 ( RIPK1 ) may participate in this signal transduction as well .
TNF-alpha/ TNFR superfamily, member 1B ( TNF-R2 ) signal transduction is mediated by a complex of intracellular signaling molecules including TNF receptor-associated factor 2 ( TRAF2 ) and RIPK1 , .
Adaptor proteins, such as FADD, TRADD and RIPK1 domain containing adaptor with death domain ( RAIDD ) transmit an activation signal to effectors caspases Caspase-2, -8, and -10 .
In other pathways, TNF/TNFRs' signal transduction is influenced via inhibition of anti-apoptotic protein members of the Bcl-2 and IAP families; e.g. B-cell CLL/lymphoma 2 ( Bcl-2 ) and BCL2-like 1 ( Bcl-XL ) baculoviral IAP repeat-containing 2 ( c-IAP1 ), baculoviral IAP repeat-containing 4 ( XIAP ).
For example, TNF superfamily, member 6 ( LIGHT )/ TNFR superfamily, member 3 ( LTBR ) signal transduction are mediated by a complex of intracellular signaling molecules including TRAF2, TNF receptor-associated factor 2 ( TRAF3 ), c-IAP1 and diablo homolog ( Smac/Diablo ) . Smac/Diablo inhibits activity of anti-apoptotic proteins c-IAP1 and XIAP .
Nerve growth factor, beta polypeptide ( NGF )/ TNFR superfamily, member 16 ( NGFR ) apoptotic signal may be mediated via different mechanisms. One such mechanism is an activation of nerve growth factor receptor associated protein 1 ( NADE ) .
TNF superfamily, member 7 ( CD70 )/ TNFR superfamily, member 7 ( CD27 ) and TNF superfamily, member 18 ( TNFSF18 )/ TNFR superfamily, member 18 ( GITR ) signal transductions are mediated by a CD27-binding (Siva) protein ( CD27BP ) , . CD27BP induces apoptosis via inhibition of anti-apoptotic proteins Bcl-2 and Bcl-XL , .
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