PMID- 16940186
OWN - NLM
STAT- MEDLINE
DCOM- 20070130
LR  - 20220331
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 26
IP  - 21
DP  - 2006 Nov
TI  - Distinct signaling pathways in TRAIL- versus tumor necrosis factor-induced 
      apoptosis.
PG  - 8136-48
AB  - Trimeric tumor necrosis factor (TNF) binding leads to recruitment of TRADD to 
      TNFR1. In current models, TRADD recruits RIP, TRAF2, and FADD to activate 
      NF-kappaB, Jun N-terminal protein kinase (JNK), and apoptosis. Using stable 
      short-hairpin RNA (shRNA) knockdown (KD) cells targeting these adaptors, TNF 
      death-inducing signaling complex immunoprecipitation demonstrates competitive 
      binding of TRADD and RIP to TNFR1, whereas TRAF2 recruitment requires TRADD. 
      Analysis of KD cells indicates that FADD is necessary for Fas-L- or TRAIL- but 
      not TNF-induced apoptosis. Interestingly, TRADD is dispensable, while RIP is 
      required for TNF-induced apoptosis in human tumor cells. TRADD is required for 
      c-Jun phosphorylation upon TNF exposure. RIP KD abrogates formation of complex II 
      following TNF exposure, whereas TRADD KD allows efficient RIP-caspase 8 
      association. Treatment with TRAIL also induces formation of a complex II 
      containing FADD, RIP, IKKalpha, and caspase 8 and 10, leading to activation of 
      caspase 8. Our data suggest that TNF triggers apoptosis in a manner distinct from 
      that of Fas-L or TRAIL.
FAU - Jin, Zhaoyu
AU  - Jin Z
AD  - Department of Medicine, University of Pennsylvania School of Medicine, 
      Philadelphia, PA 19104, USA.
FAU - El-Deiry, Wafik S
AU  - El-Deiry WS
LA  - eng
GR  - P01 CA098101/CA/NCI NIH HHS/United States
GR  - R01 CA097100/CA/NCI NIH HHS/United States
GR  - CA097110/CA/NCI NIH HHS/United States
GR  - CA098101/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060828
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fas-Associated Death Domain Protein)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (TNF Receptor-Associated Death Domain Protein)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Apoptosis/*physiology
MH  - Caspases/metabolism
MH  - Cell Line
MH  - Fas Ligand Protein/genetics/metabolism
MH  - Fas-Associated Death Domain Protein/genetics/metabolism
MH  - Humans
MH  - Nucleic Acid Conformation
MH  - RNA/chemistry/genetics/metabolism
MH  - RNA Interference
MH  - Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor, Type I/genetics/metabolism
MH  - Signal Transduction/*physiology
MH  - TNF Receptor-Associated Death Domain Protein/genetics/metabolism
MH  - TNF Receptor-Associated Factor 2/genetics/metabolism
MH  - TNF-Related Apoptosis-Inducing Ligand/genetics/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
PMC - PMC1636728
EDAT- 2006/08/31 09:00
MHDA- 2007/01/31 09:00
PMCR- 2007/03/01
CRDT- 2006/08/31 09:00
PHST- 2006/08/31 09:00 [pubmed]
PHST- 2007/01/31 09:00 [medline]
PHST- 2006/08/31 09:00 [entrez]
PHST- 2007/03/01 00:00 [pmc-release]
AID - MCB.00257-06 [pii]
AID - 0257-06 [pii]
AID - 10.1128/MCB.00257-06 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2006 Nov;26(21):8136-48. doi: 10.1128/MCB.00257-06. Epub 2006 Aug 
      28.