APOPTOTIC, NON-APOPTOTIC, AND ANTI-APOPTOTIC PATHWAYS OF TUMOR-NECROSIS-FACTOR SIGNALING

Citation
G. Natoli et al., APOPTOTIC, NON-APOPTOTIC, AND ANTI-APOPTOTIC PATHWAYS OF TUMOR-NECROSIS-FACTOR SIGNALING, Biochemical pharmacology, 56(8), 1998, pp. 915-920
Citations number
49
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
00062952
Volume
56
Issue
8
Year of publication
1998
Pages
915 - 920
Database
ISI
SICI code
0006-2952(1998)56:8<915:ANAAPO>2.0.ZU;2-P
Abstract
Early events in the signalling of tumor necrosis factor-receptor 1 (TN F-R1), which is the main TNF receptor on most cell types, have been cl arified recently. A multimolecular signal transducing complex from whi ch several pathways originate rapidly forms upon TNF-induced aggregati on of the receptor. Although fully capable of transducing apoptotic si gnals, 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 indu ction of a complex cytoprotective response that requires TNF-receptor associated factor 2 (TRAF2), a signal transducer that couples TNF-R1 t o both nuclear factor kappa B (NF kappa B)-dependent and NF kappa B-in dependent transcriptional events implicated in induction of genes prot ecting from TNF cytotoxicity. Although absolutely required for cytopro tection, TNF-receptor associated factor 2 is not sufficient to protect cells from TNF, thus suggesting that it may act in concert with addit ional TNF-R1 complex components. In this commentary, we will discuss s ome critical aspects of TNF-R1 signal transduction that are not fully understood: Why do cells not die before the protective protein synthes is has occurred! What are the mechanisms implicated in the termination of each TNF-R1-elicited response! Are there regulatory mechanisms cap able of influencing the composition of the TNF-R1 complex and, consequ ently, the propagation of specific signals! (C) 1998 Elsevier Science Inc.