Cellular prion protein inhibits proapoptotic Bax conformational change in human neurons and in breast carcinoma MCF-7 cells

Cell Death Differ. 2005 Jul;12(7):783-95. doi: 10.1038/sj.cdd.4401629.


Prion protein (PrP) prevents Bcl-2-associated protein X (Bax)-mediated cell death, but the step at which PrP inhibits is not known. We first show that PrP is very specific for Bax and cannot prevent Bak (Bcl-2 antagonist killer 1)-, tBid-, staurosporine- or thapsigargin-mediated cell death. As Bax activation involves Bax conformational change, mitochondrial translocation, cytochrome c release and caspase activation, we investigated which of these events was inhibited by PrP. PrP inhibits Bax conformational change, cytochrome c release and cell death in human primary neurons and MCF-7 cells. Serum deprivation-induced Bax conformational change is more rapid in PrP-null cells. PrP does not prevent active caspase-mediated cell death. PrP does not colocalize with Bax in normal or apoptotic primary neurons and cannot prevent Bax-mediated cytochrome c release in a mitochondrial cell-free system. We conclude that PrP protects against Bax-mediated cell death by preventing the Bax proapoptotic conformational change that occurs initially in Bax activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis* / drug effects
  • BH3 Interacting Domain Death Agonist Protein
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carrier Proteins / metabolism
  • Caspase 6
  • Cell Line, Tumor
  • Cysteine Endopeptidases / metabolism
  • Cytochromes c / metabolism
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism
  • Neurons / drug effects
  • Neurons / metabolism*
  • PrPC Proteins / metabolism*
  • Protein Structure, Quaternary
  • Protein Transport / drug effects
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors
  • Proto-Oncogene Proteins c-bcl-2 / chemistry*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Thapsigargin / pharmacology
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein


  • BAK1 protein, human
  • BAX protein, human
  • BH3 Interacting Domain Death Agonist Protein
  • BID protein, human
  • Carrier Proteins
  • Enzyme Inhibitors
  • Membrane Proteins
  • PrPC Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • Thapsigargin
  • Cytochromes c
  • CASP6 protein, human
  • Caspase 6
  • Cysteine Endopeptidases