The NF-kappaB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease

Cell Death Differ. 2006 May;13(5):712-29. doi: 10.1038/sj.cdd.4401865.


NF-kappaB/Rel transcription factors have recently emerged as crucial regulators of cell survival. Activation of NF-kappaB antagonizes programmed cell death (PCD) induced by tumor necrosis factor-receptors (TNF-Rs) and several other triggers. This prosurvival activity of NF-kappaB participates in a wide range of biological processes, including immunity, lymphopoiesis and development. It is also crucial for pathogenesis of various cancers, chronic inflammation and certain hereditary disorders. This participation of NF-kappaB in survival signaling often involves an antagonism of PCD triggered by TNF-R-family receptors, and is mediated through a suppression of the formation of reactive oxygen species (ROS) and a control of sustained activation of the Jun-N-terminal kinase (JNK) cascade. Effectors of this antagonistic activity of NF-kappaB on this ROS/JNK pathway have been recently identified. Indeed, further delineating the mechanisms by which NF-kappaB promotes cell survival might hold the key to developing new highly effective therapies for treatment of widespread human diseases.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Apoptosis*
  • Disease*
  • Evolution, Molecular
  • Gene Expression Regulation*
  • Health*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Models, Biological
  • NF-kappa B / metabolism
  • NF-kappa B / physiology*
  • Necrosis
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Reactive Oxygen Species / metabolism
  • Receptors, Tumor Necrosis Factor / physiology
  • Signal Transduction
  • Tumor Necrosis Factor-alpha / pharmacology


  • NF-kappa B
  • Reactive Oxygen Species
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • JNK Mitogen-Activated Protein Kinases