Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor signalling

G. Natoli, A. Costanzo, F. Guido, F. Moretti, M. Levrero

Research output: Contribution to journalArticle

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 κB (NFκB)-dependent and NFκB-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? Copyright (C) 1998 Elsevier Science Inc.

Original languageEnglish
Pages (from-to)915-920
Number of pages6
JournalBiochemical Pharmacology
Volume56
Issue number8
DOIs
Publication statusPublished - 1998

Fingerprint

Tumor Necrosis Factor Receptors
Tumor Necrosis Factor-alpha
TNF Receptor-Associated Factor 2
Fas-Associated Death Domain Protein
Receptor Aggregation
Signal transduction
Cytoprotection
Cytotoxicity
Transducers
Signal Transduction
Peptide Hydrolases
Agglomeration
Genes
Chemical activation
Chemical analysis

Keywords

  • NFκB/Rel family
  • TRAF family
  • Tumor necrosis factor
  • Tumor necrosis factor receptors

ASJC Scopus subject areas

  • Pharmacology

Cite this

Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor signalling. / Natoli, G.; Costanzo, A.; Guido, F.; Moretti, F.; Levrero, M.

In: Biochemical Pharmacology, Vol. 56, No. 8, 1998, p. 915-920.

Research output: Contribution to journalArticle

Natoli, G. ; Costanzo, A. ; Guido, F. ; Moretti, F. ; Levrero, M. / Apoptotic, non-apoptotic, and anti-apoptotic pathways of tumor necrosis factor signalling. In: Biochemical Pharmacology. 1998 ; Vol. 56, No. 8. pp. 915-920.
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