Induction of cell death by tumour necrosis factor (TNF) receptor 2, CD40 and CD30: A role for TNF-R1 activation by endogenous membrane-anchored TNF

Matthias Grell*, Gudrun Zimmermann, Eva Gottfried, Chun Ming Chen, Uli Grünwald, David C.S. Huang, Yan-Hwa Wu Lee, Horst Dürkop, Hartmut Engelmann, Peter Scheurich, Harald Wajant, Andreas Strasser

*Corresponding author for this work

Research output: Contribution to journalArticle

248 Scopus citations

Abstract

Several members of the tumour necrosis factor receptor (TNF-R) superfamily can induce cell death. For TNF-R1, Fas/APO-1, DR3, DR6, TRAIL-R1 and TRAIL-R2, a conserved 'death domain' in the intracellular region couples these receptors to activation of caspases. However, it is not yet known how TNF receptor family members lacking a death domain, such as TNF-R2, CD40, LT-βR, CD27 or CD30, execute their death-inducing capability. Here we demonstrate in different cellular systems that cytotoxic effects induced by TNF-R2, CD40 and CD30 are mediated by endogenous production of TNF and autotropic or paratropic activation of TNF-R1. In addition, stimulation of TNF-R2 and CD40 synergistically enhances TNF-R1-induced cytotoxicity. These findings describe a novel pro-apoptotic mechanism induced by some members of the TNF-R family.

Original languageEnglish
Pages (from-to)3034-3043
Number of pages10
JournalEMBO Journal
Volume18
Issue number11
DOIs
StatePublished - 1 Jun 1999

Keywords

  • Apoptosis
  • Bcl-2
  • Bcl-x(L)
  • CrmA
  • TNF receptor

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    Grell, M., Zimmermann, G., Gottfried, E., Chen, C. M., Grünwald, U., Huang, D. C. S., Wu Lee, Y-H., Dürkop, H., Engelmann, H., Scheurich, P., Wajant, H., & Strasser, A. (1999). Induction of cell death by tumour necrosis factor (TNF) receptor 2, CD40 and CD30: A role for TNF-R1 activation by endogenous membrane-anchored TNF. EMBO Journal, 18(11), 3034-3043. https://doi.org/10.1093/emboj/18.11.3034