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
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
(GITRL)/ 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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