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

doi:10.1093/emboj/18.11.3034

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

Department of Biological Science and Technology

Research output: Contribution to journal › Article › peer-review

260 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 language	English
Pages (from-to)	3034-3043
Number of pages	10
Journal	EMBO Journal
Volume	18
Issue number	11
DOIs	https://doi.org/10.1093/emboj/18.11.3034
State	Published - 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

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title = "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",

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.",

keywords = "Apoptosis, Bcl-2, Bcl-x(L), CrmA, TNF receptor",

author = "Matthias Grell and Gudrun Zimmermann and Eva Gottfried and Chen, {Chun Ming} and Uli Gr{\"u}nwald and Huang, {David C.S.} and {Wu Lee}, Yan-Hwa and Horst D{\"u}rkop and Hartmut Engelmann and Peter Scheurich and Harald Wajant and Andreas Strasser",

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Grell, M, Zimmermann, G, Gottfried, E, Chen, CM, Grünwald, U, Huang, DCS, 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, vol. 18, no. 11, pp. 3034-3043. https://doi.org/10.1093/emboj/18.11.3034

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AU - Grell, Matthias

AU - Zimmermann, Gudrun

AU - Gottfried, Eva

AU - Chen, Chun Ming

AU - Grünwald, Uli

AU - Huang, David C.S.

AU - Wu Lee, Yan-Hwa

AU - Dürkop, Horst

AU - Engelmann, Hartmut

AU - Scheurich, Peter

AU - Wajant, Harald

AU - Strasser, Andreas

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N2 - 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.

AB - 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.

KW - Apoptosis

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KW - Bcl-x(L)

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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

Abstract

Keywords

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