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.
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-betaR, 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.
Grell
M
M
Institute of Cell Biology and Immunology, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Zimmermann
G
G
Gottfried
E
E
Chen
C M
CM
Grünwald
U
U
Huang
D C
DC
Wu Lee
Y H
YH
Dürkop
H
H
Engelmann
H
H
Scheurich
P
P
Wajant
H
H
Strasser
A
A
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D019013:CD40 Antigens / Q000235:genetics / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D053222:Fas Ligand Protein; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017730:Ki-1 Antigen / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D051020:bcl-X Protein; D000096743:Interferon gamma Receptor
D000906:Antibodies; D015703:Antigens, CD; D019013:CD40 Antigens; D061945:Caspase Inhibitors; D020169:Caspases; D053222:Fas Ligand Protein; D007371:Interferon-gamma; D017730:Ki-1 Antigen; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D017471:Receptors, Interferon; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D000096743:Interferon gamma Receptor; C494811:BCL2L1 protein, human; C494812:Bcl2l1 protein, mouse; C505661:FASLG protein, human; C505658:Fasl protein, mouse