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) [1], [2], [3].
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 [3].
Apoptotic signals from TNFR superfamily, member 1A
(TNF-R1) [4], TNFR superfamily, member 12
(DR3) [5], TNFR superfamily, member 10a
(DR4) [6], TNFR superfamily, member 10b
(DR5) [7] and, possibly, TNFR superfamily,
member 21 (DR6) [7] 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 [8].
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 [9], [10].
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 [11].
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) [12].
Smac/Diablo inhibits activity of anti-apoptotic proteins
c-IAP1 and XIAP [13].
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) [14].
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) [15], [16].
CD27BP induces apoptosis via inhibition of anti-apoptotic
proteins Bcl-2 and Bcl-XL
[17], [18].
References:
- Darnay BG, Aggarwal BB
Signal transduction by tumour necrosis factor and tumour necrosis factor related ligands and their receptors.
Annals of the rheumatic diseases 1999 Nov;58 Suppl 1:I2-I13
- Beletsky IP, Moshnikova AB, Proussakova OV
Cytotoxic signal transduction pathways via TNF family receptors.
Biochemistry. Biokhimiia 2002 Mar;67(3):312-28
- Lavrik I, Golks A, Krammer PH
Death receptor signaling.
Journal of cell science 2005 Jan 15;118(Pt 2):265-7
- Baud V, Karin M
Signal transduction by tumor necrosis factor and its relatives.
Trends in cell biology 2001 Sep;11(9):372-7
- Chinnaiyan AM, O'Rourke K, Yu GL, Lyons RH, Garg M, Duan DR, Xing L, Gentz R, Ni J, Dixit VM
Signal transduction by DR3, a death domain-containing receptor related to TNFR-1 and CD95.
Science (New York, N.Y.) 1996 Nov 8;274(5289):990-2
- Chaudhary PM, Eby M, Jasmin A, Bookwalter A, Murray J, Hood L
Death receptor 5, a new member of the TNFR family, and DR4 induce FADD-dependent apoptosis and activate the NF-kappaB pathway.
Immunity 1997 Dec;7(6):821-30
- Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A
Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5.
Immunity 2000 Jun;12(6):611-20
- Meylan E, Tschopp J
The RIP kinases: crucial integrators of cellular stress.
Trends in biochemical sciences 2005 Mar;30(3):151-9
- Pimentel-Mui?os FX, Seed B
Regulated commitment of TNF receptor signaling: a molecular switch for death or activation.
Immunity 1999 Dec;11(6):783-93
- MacEwan DJ
TNF ligands and receptors--a matter of life and death.
British journal of pharmacology 2002 Feb;135(4):855-75
- Riedl SJ, Shi Y
Molecular mechanisms of caspase regulation during apoptosis.
Nature reviews. Molecular cell biology 2004 Nov;5(11):897-907
- Kuai J, Nickbarg E, Wooters J, Qiu Y, Wang J, Lin LL
Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis.
The Journal of biological chemistry 2003 Apr 18;278(16):14363-9
- Verhagen AM, Ekert PG, Pakusch M, Silke J, Connolly LM, Reid GE, Moritz RL, Simpson RJ, Vaux DL
Identification of DIABLO, a mammalian protein that promotes apoptosis by binding to and antagonizing IAP proteins.
Cell 2000 Jul 7;102(1):43-53
- Mukai J, Hachiya T, Shoji-Hoshino S, Kimura MT, Nadano D, Suvanto P, Hanaoka T, Li Y, Irie S, Greene LA, Sato TA
NADE, a p75NTR-associated cell death executor, is involved in signal transduction mediated by the common neurotrophin receptor p75NTR.
The Journal of biological chemistry 2000 Jun 9;275(23):17566-70
- Spinicelli S, Nocentini G, Ronchetti S, Krausz LT, Bianchini R, Riccardi C
GITR interacts with the pro-apoptotic protein Siva and induces apoptosis.
Cell death and differentiation 2002 Dec;9(12):1382-4
- Py B, Slomianny C, Auberger P, Petit PX, Benichou S
Siva-1 and an alternative splice form lacking the death domain, Siva-2, similarly induce apoptosis in T lymphocytes via a caspase-dependent mitochondrial pathway.
Journal of immunology (Baltimore, Md. : 1950) 2004 Apr 1;172(7):4008-17
- Xue L, Chu F, Cheng Y, Sun X, Borthakur A, Ramarao M, Pandey P, Wu M, Schlossman SF, Prasad KV
Siva-1 binds to and inhibits BCL-X(L)-mediated protection against UV radiation-induced apoptosis.
Proceedings of the National Academy of Sciences of the United States of America 2002 May 14;99(10):6925-30
- Chu F, Borthakur A, Sun X, Barkinge J, Gudi R, Hawkins S, Prasad KV
The Siva-1 putative amphipathic helical region (SAH) is sufficient to bind to BCL-XL and sensitize cells to UV radiation induced apoptosis.
Apoptosis : an international journal on programmed cell death 2004 Jan;9(1):83-95