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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
Author(s) -
Grell Matthias,
Zimmermann Gudrun,
Gottfried Eva,
Chen ChunMing,
Grünwald Uli,
Huang David C.S.,
Lee YanHwa Wu,
Dürkop Horst,
Engelmann Hartmut,
Scheurich Peter,
Wajant Harald,
Strasser Andreas
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.11.3034
Subject(s) - tumor necrosis factor alpha , biology , endogeny , cd30 , tumor necrosis factor receptor , receptor , microbiology and biotechnology , tumor necrosis factors , cell surface receptor , lymphotoxin beta receptor , cancer research , immunology , tumor cells , biochemistry
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.