Dissection of TNF Receptor 1 Effector Functions: JNK Activation Is Not Linked to Apoptosis While NF-kappaB Activation Prevents Cell Death

Cell. 1996 Nov 1;87(3):565-76. doi: 10.1016/s0092-8674(00)81375-6.

Abstract

Through its type 1 receptor (TNFR1), the cytokine TNF elicits an unusually wide range of biological responses, including inflammation, tumor necrosis, cell proliferation, differentiation, and apoptosis. We investigated how TNFR1 activates different effector functions; the protein kinase JNK, transcription factor NF-kappaB, and apoptosis. We found that the three responses are mediated through separate pathways. Recruitment of the signal transducer FADD to the TNFR1 complex mediates apoptosis but not NF-kappaB or JNK activation. Two other signal transducers, RIP and TRAF2, mediate both JNK and NF-kappaB activation. These two responses, however, diverge downstream to TRAF2. Most importantly, JNK activation is not involved in induction of apoptosis, while activation of NF-kappaB protects against TNF-induced apoptosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / pathology
  • Antigens, CD / physiology*
  • Apoptosis / physiology*
  • Arabidopsis Proteins*
  • Breast Neoplasms / pathology
  • Enzyme Activation
  • Fatty Acid Desaturases / physiology
  • Female
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases*
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases*
  • NF-kappa B / physiology*
  • Neoplasm Proteins / physiology
  • Phosphorylation
  • Plant Proteins / physiology
  • Protein Kinases / physiology*
  • Protein Processing, Post-Translational*
  • Receptors, Tumor Necrosis Factor / physiology*
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Antigens, CD
  • Arabidopsis Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Plant Proteins
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Recombinant Fusion Proteins
  • Tumor Necrosis Factor-alpha
  • Fatty Acid Desaturases
  • Fad7 protein, Arabidopsis
  • Protein Kinases
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • Mitogen-Activated Protein Kinase Kinases