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Knock-out of the neural death effector domain protein PEA-15 demonstrates that its expression protects astrocytes from TNFalpha-induced apoptosis.

Apoptosis is a very general phenomenon, but only a few reports concern astrocytes. Indeed, astrocytes express receptors for tumor necrosis factor (TNF) alpha, a cytokine demonstrated on many cells and tissues to mediate apoptosis after recruitment of adaptor proteins containing a death effector domain (DED). PEA-15 is a DED-containing protein prominently expressed in the CNS and particularly abundant in astrocytes. This led us to investigate if PEA-15 expression could be involved in astrocytic protection against deleterious effects of TNF. In vitro assays evidence that PEA-15 may bind to DED-containing protein FADD and caspase-8 known to be apical adaptors of the TNF apoptotic signaling. After generation of PEA-15 null mutant mice, our results demonstrate that PEA-15 expression increases astrocyte survival after exposure to TNF.

Pubmed ID: 10493725


  • Kitsberg D
  • Formstecher E
  • Fauquet M
  • Kubes M
  • Cordier J
  • Canton B
  • Pan G
  • Rolli M
  • Glowinski J
  • Chneiweiss H


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

October 1, 1999

Associated Grants


Mesh Terms

  • Amino Acid Sequence
  • Animals
  • Apoptosis
  • Arabidopsis Proteins
  • Astrocytes
  • Caspase 8
  • Caspase 9
  • Caspases
  • Cells, Cultured
  • Corpus Striatum
  • Embryo, Mammalian
  • Fatty Acid Desaturases
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Neuroglia
  • Phosphoproteins
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Tumor Necrosis Factor-alpha