JNK/SAPK activity contributes to TRAIL-induced apoptosis

Cell Death Differ. 1999 Feb;6(2):130-5. doi: 10.1038/sj.cdd.4400467.

Abstract

We report here that JNK/SAPKs are activated by TRAIL in parallel to induction of apoptosis in human T and B cell lines. Death signaling as well as JNK/SAPK activation by TRAIL in these cells is FADD- and caspase-dependent since dominant-negative FADD or the caspase inhibitor zVAD prevented both, apoptosis and JNK/SAPK activity. JNK/SAPK activity in response to triggering of CD95 by an agonistic antibody (alphaAPO-1) was also diminished by dominant-negative FADD or zVAD. Correspondingly, a cell line resistant to alphaAPO-1-induced death exhibited crossresistance to TRAIL-induced apoptosis and did not upregulate JNK/SAPK activity in response to TRAIL or alphaAPO-1. Inhibition of JNK/SAPK activity, by stably transfecting cells with a dominant-negative JNKK-MKK4 construct, reduced apoptosis in response to TRAIL or alphaAPO-1. Therefore, activation of JNK/SAPKs by TRAIL or alphaAPO-1 occurs downstream of FADD and caspases and contributes to apoptosis in human lymphoid cell lines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies / pharmacology
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Arabidopsis Proteins*
  • B-Lymphocytes / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
  • Caspases / metabolism
  • Cell Line
  • Enzyme Activation
  • Enzyme Inhibitors / pharmacology
  • Fatty Acid Desaturases / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Membrane Glycoproteins / metabolism*
  • Mitogen-Activated Protein Kinase Kinases*
  • Mitogen-Activated Protein Kinases*
  • Pichia / genetics
  • Plant Proteins / metabolism
  • Protein Kinases / genetics
  • Signal Transduction / physiology
  • T-Lymphocytes / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Transfection
  • Tumor Necrosis Factor-alpha / metabolism*
  • fas Receptor / immunology

Substances

  • Antibodies
  • Apoptosis Regulatory Proteins
  • Arabidopsis Proteins
  • Enzyme Inhibitors
  • Membrane Glycoproteins
  • Plant Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Necrosis Factor-alpha
  • fas Receptor
  • Fatty Acid Desaturases
  • Fad7 protein, Arabidopsis
  • Protein Kinases
  • Calcium-Calmodulin-Dependent Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases
  • Caspases