PMID- 12721308
OWN - NLM
STAT- MEDLINE
DCOM- 20030814
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 28
DP  - 2003 Jul 11
TI  - Fas-associated death domain protein and caspase-8 are not recruited to the tumor 
      necrosis factor receptor 1 signaling complex during tumor necrosis factor-induced 
      apoptosis.
PG  - 25534-41
AB  - Death receptors are a subfamily of the tumor necrosis factor (TNF) receptor 
      subfamily. They are characterized by a death domain (DD) motif within their 
      intracellular domain, which is required for the induction of apoptosis. 
      Fas-associated death domain protein (FADD) is reported to be the universal 
      adaptor used by death receptors to recruit and activate the initiator caspase-8. 
      CD95, TNF-related apoptosis-inducing ligand (TRAIL-R1), and TRAIL-R2 bind FADD 
      directly, whereas recruitment to TNF-R1 is indirect through another adaptor TNF 
      receptor-associated death domain protein (TRADD). TRADD also binds two other 
      adaptors receptor-interacting protein (RIP) and TNF-receptor-associated factor 2 
      (TRAF2), which are required for TNF-induced NF-kappaB and c-Jun N-terminal kinase 
      activation, respectively. Analysis of the native TNF signaling complex revealed 
      the recruitment of RIP, TRADD, and TRAF2 but not FADD or caspase-8. TNF failed to 
      induce apoptosis in FADD- and caspase-8-deficient Jurkat cells, indicating that 
      these apoptotic mediators were required for TNF-induced apoptosis. In an in vitro 
      binding assay, the intracellular domain of TNF-R1 bound TRADD, RIP, and TRAF2 but 
      did not bind FADD or caspase-8. Under the same conditions, the intracellular 
      domain of both CD95 and TRAIL-R2 bound both FADD and caspase-8. Taken together 
      these results suggest that apoptosis signaling by TNF is distinct from that 
      induced by CD95 and TRAIL. Although caspase-8 and FADD are obligatory for 
      TNF-mediated apoptosis, they are not recruited to a TNF-induced membrane-bound 
      receptor signaling complex as occurs during CD95 or TRAIL signaling, but instead 
      must be activated elsewhere within the cell.
FAU - Harper, Nicholas
AU  - Harper N
AD  - Medical Research Council Toxicology Unit, Hodgkin Building, University of 
      Leicester, P.O. Box 138, Lancaster Road, Leicester, LE1 9HN, United Kingdom.
FAU - Hughes, Michelle
AU  - Hughes M
FAU - MacFarlane, Marion
AU  - MacFarlane M
FAU - Cohen, Gerald M
AU  - Cohen GM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030429
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Annexin A5)
RN  - 0 (Antigens, CD)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Carrier Proteins)
RN  - 0 (FADD protein, human)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 0 (TNF Receptor-Associated Factor 1)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (TNFSF10 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (fas Receptor)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 3.4.22.- (CASP8 protein, human)
RN  - EC 3.4.22.- (CASP9 protein, human)
RN  - EC 3.4.22.- (Caspase 8)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Annexin A5/pharmacology
MH  - Antigens, CD/*metabolism
MH  - *Apoptosis
MH  - Apoptosis Regulatory Proteins
MH  - Blotting, Western
MH  - Carrier Proteins/*metabolism
MH  - Caspase 8
MH  - Caspase 9
MH  - Caspases/metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Fas-Associated Death Domain Protein
MH  - Glutathione Transferase/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Jurkat Cells
MH  - Membrane Glycoproteins/metabolism
MH  - NF-kappa B/metabolism
MH  - Protein Binding
MH  - Protein Structure, Tertiary
MH  - Proteins/metabolism
MH  - Receptors, Tumor Necrosis Factor/*metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Recombinant Fusion Proteins/metabolism
MH  - Recombinant Proteins/metabolism
MH  - *Signal Transduction
MH  - TNF Receptor-Associated Factor 1
MH  - TNF Receptor-Associated Factor 2
MH  - TNF-Related Apoptosis-Inducing Ligand
MH  - Time Factors
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - U937 Cells
MH  - fas Receptor/metabolism
EDAT- 2003/05/02 05:00
MHDA- 2003/08/15 05:00
CRDT- 2003/05/02 05:00
PHST- 2003/05/02 05:00 [pubmed]
PHST- 2003/08/15 05:00 [medline]
PHST- 2003/05/02 05:00 [entrez]
AID - S0021-9258(19)75067-4 [pii]
AID - 10.1074/jbc.M303399200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Jul 11;278(28):25534-41. doi: 10.1074/jbc.M303399200. Epub 2003 
      Apr 29.