Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor signalling.
Biochem Pharmacol
; 56(8): 915-20, 1998 Oct 15.
Article
en En
| MEDLINE
| ID: mdl-9776301
ABSTRACT
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?
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Transducción de Señal
/
Antígenos CD
/
Factor de Necrosis Tumoral alfa
/
Apoptosis
/
Receptores del Factor de Necrosis Tumoral
/
Proteínas de Arabidopsis
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Pharmacol
Año:
1998
Tipo del documento:
Article
País de afiliación:
Italia