FADD/MORT1 and caspase-8 Are Recruited to TRAIL Receptors 1 and 2 and Are Essential for Apoptosis Mediated by TRAIL Receptor 2

Immunity. 2000 Jun;12(6):599-609. doi: 10.1016/s1074-7613(00)80211-3.

Abstract

Apoptosis induced by tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/APO-2L) has been shown to exert important functions during various immunological processes. The involvement of the death adaptor proteins FADD/MORT1, TRADD, and RIP and the apoptosis-initiating caspases-8 and -10 in death signaling by the two death-inducing TRAIL receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) are controversial. Analysis of the native TRAIL death-inducing signaling complex (DISC) revealed ligand-dependent recruitment of FADD/MORT1 and caspase-8. Differential precipitation of ligand-stimulated TRAIL receptors demonstrated that FADD/MORT1 and caspase-8 were recruited to TRAIL-R1 and TRAIL-R2 independently of each other. FADD/MORT1- and caspase-8-deficient Jurkat cells expressing only TRAIL-R2 were resistant to TRAIL-induced apoptosis. Thus, FADD/MORT1 and caspase-8 are essential for apoptosis induction via TRAIL-R2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Apoptosis / immunology*
  • B-Lymphocytes / cytology
  • B-Lymphocytes / enzymology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism
  • Caspases / physiology*
  • Cell Line
  • Fas-Associated Death Domain Protein
  • Humans
  • Jurkat Cells
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Receptors, Tumor Necrosis Factor / physiology*
  • Signal Transduction / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / enzymology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Tumor Cells, Cultured
  • fas Receptor / physiology*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • FADD protein, human
  • Fas-Associated Death Domain Protein
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • TNFRSF10A protein, human
  • TNFRSF10B protein, human
  • fas Receptor
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 8
  • Caspase 9
  • Caspases