Death-inducing functions of ligands of the tumor necrosis factor family: a Sanhedrin verdict.
Members of the tumor necrosis factor ligand family can kill cells in a rather straightforward manner. They induce their receptors to recruit and activate caspases, enzymes that are critically involved in the death process, and this activation is further amplified by intracellular mitochondria-associated mechanisms. The potentially hazardous expression of the ligands occurs widely in the body; it is antigen-restricted only in the lymphocytes. Yet, in addition to control modes affecting ligand expression, there are numerous inhibitory mechanisms that act within target cells, to make doubly sure of avoiding an undue 'death verdict', while allowing the cells to exhibit other, noncytocidal effects of the ligands.
Wallach
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D
Department of Biological Chemistry, Weizmann Institute, Rehovot, Israel.
Kovalenko
A V
AV
Varfolomeev
E E
EE
Boldin
M P
MP
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D029681:Arabidopsis Proteins; D053420:CRADD Signaling Adaptor Protein; D002352:Carrier Proteins / Q000502:physiology; D002470:Cell Survival; D017077:Culture Media, Conditioned; D003546:Cysteine Endopeptidases / Q000502:physiology; D015853:Cysteine Proteinase Inhibitors / Q000502:physiology; D053938:DNA Fragmentation; D053200:Fas-Associated Death Domain Protein; D044943:Fatty Acid Desaturases / Q000502:physiology; D006801:Humans; D008024:Ligands; D008928:Mitochondria / Q000502:physiology; D008954:Models, Biological; D005810:Multigene Family; D010940:Plant Proteins / Q000502:physiology; D011506:Proteins / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D017475:Receptors, Nerve Growth Factor / Q000187:drug effects / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000145:classification / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology
D048868:Adaptor Proteins, Signal Transducing; D029681:Arabidopsis Proteins; D053420:CRADD Signaling Adaptor Protein; C104252:CRADD protein, human; D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D015853:Cysteine Proteinase Inhibitors; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D008024:Ligands; D010940:Plant Proteins; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D044943:Fatty Acid Desaturases; C084083:Fad7 protein, Arabidopsis; C506249:RIPK1 protein, human; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; D003546:Cysteine Endopeptidases