title: Cell death-independent activities of the death receptors CD95, TRAILR1, and TRAILR2.
abstract: Since their identification more than 20 years ago, the death receptors CD95, TRAILR1, and TRAILR2 have been intensively studied with respect to their cell death-inducing activities. These receptors, however, can also trigger a variety of cell death-independent cellular responses reaching from the activation of proinflammatory gene transcription programs over the stimulation of proliferation and differentiation to induction of cell migration. The cell death-inducing signaling mechanisms of CD95 and the TRAIL death receptors are well understood. In contrast, despite the increasing recognition of the biological and pathophysiological relevance of the cell death-independent activities of CD95, TRAILR1, and TRAILR2, the corresponding signaling mechanisms are less understood and give no fully coherent picture. This review is focused on the cell death-independent activities of CD95 and the TRAIL death receptors and addresses mainly three questions: (a) how are these receptors linked to noncell death pathways at the molecular level, (b) which factors determine the balance of cell death and cell death-independent activities of CD95 and the TRAIL death receptors at the cellular level, and (c) what are the consequences of the cell death-independent functions of these receptors for their role in cancer and inflammatory diseases.
authors.affiliation: Division of Molecular Internal Medicine, Medical Clinic and Polyclinic II, University Hospital Würzburg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Siegmund
authors.affiliation: Division of Molecular Internal Medicine, Medical Clinic and Polyclinic II, University Hospital Würzburg, Germany.
authors.forename: Isabell
authors.initials: I
authors.lastname: Lang
authors.affiliation: Division of Molecular Internal Medicine, Medical Clinic and Polyclinic II, University Hospital Würzburg, Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Wajant
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D004789:Enzyme Activation; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology*
chemical_list: C491901:FAS protein, human; D016328:NF-kappa B; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; D019014:fas Receptor; D020928:Mitogen-Activated Protein Kinases; D020169:Caspases
keywords: 
  TRAIL
  ; CD95; NF-kappaB; RIP1; apoptosis; caspase-8; cell migration; death receptors; necroptosis