PMID- 9776301
OWN - NLM
STAT- MEDLINE
DCOM- 19981022
LR  - 20211110
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 56
IP  - 8
DP  - 1998 Oct 15
TI  - Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor 
      signalling.
PG  - 915-20
AB  - Early events in the signalling of tumor necrosis factor-receptor 1 (TNF-R1), 
      which is the main TNF receptor on most cell types, have been clarified recently. 
      A multimolecular signal transducing complex from which several pathways originate 
      rapidly forms upon TNF-induced aggregation of the receptor. Although fully 
      capable of transducing apoptotic signals, which depend on the adapter 
      Fas-associated death domain protein (FADD) and on the subsequent 
      recruitment/activation of the apoptotic proteases, TNF-R1 usually does not kill 
      cells; this is due to the induction of a complex cytoprotective response that 
      requires TNF-receptor associated factor 2 (TRAF2), a signal transducer that 
      couples TNF-R1 to both nuclear factor kappaB (NFkappaB)-dependent and 
      NFkappaB-independent transcriptional events implicated in induction of genes 
      protecting from TNF cytotoxicity. Although absolutely required for 
      cytoprotection, TNF-receptor associated factor 2 is not sufficient to protect 
      cells from TNF, thus suggesting that it may act in concert with additional TNF-R1 
      complex components. In this commentary, we will discuss some critical aspects of 
      TNF-R1 signal transduction that are not fully understood: Why do cells not die 
      before the protective protein synthesis has occurred? What are the mechanisms 
      implicated in the termination of each TNF-R1-elicited response? Are there 
      regulatory mechanisms capable of influencing the composition of the TNF-R1 
      complex and, consequently, the propagation of specific signals?
FAU - Natoli, G
AU  - Natoli G
AD  - Fondazione Andrea Cesalpino and Istituto I Clinica Medica, Universita degli Studi 
      di Roma La Sapienza, Rome, Italy. levmax@mix.it
FAU - Costanzo, A
AU  - Costanzo A
FAU - Guido, F
AU  - Guido F
FAU - Moretti, F
AU  - Moretti F
FAU - Levrero, M
AU  - Levrero M
LA  - eng
PT  - Journal Article
PT  - Review
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antigens, CD)
RN  - 0 (Arabidopsis Proteins)
RN  - 0 (Plant Proteins)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.19.- (Fatty Acid Desaturases)
RN  - EC 1.14.99.- (Fad7 protein, Arabidopsis)
SB  - IM
MH  - Animals
MH  - Antigens, CD/*physiology
MH  - Apoptosis/*physiology
MH  - *Arabidopsis Proteins
MH  - Cell Death/physiology
MH  - Cytoprotection
MH  - Fatty Acid Desaturases/physiology
MH  - Humans
MH  - Plant Proteins/physiology
MH  - Proteins/physiology
MH  - Receptors, Tumor Necrosis Factor/*physiology
MH  - Receptors, Tumor Necrosis Factor, Type I
MH  - Signal Transduction/*physiology
MH  - TNF Receptor-Associated Factor 2
MH  - Tumor Necrosis Factor-alpha/*physiology
RF  - 49
EDAT- 1998/10/17 00:00
MHDA- 1998/10/17 00:01
CRDT- 1998/10/17 00:00
PHST- 1998/10/17 00:00 [pubmed]
PHST- 1998/10/17 00:01 [medline]
PHST- 1998/10/17 00:00 [entrez]
AID - S0006-2952(98)00154-3 [pii]
AID - 10.1016/s0006-2952(98)00154-3 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 1998 Oct 15;56(8):915-20. doi: 10.1016/s0006-2952(98)00154-3.