Bcl-2 antiapoptotic protein mediates verotoxin II-induced cell death: possible association between bcl-2 and tissue failure by E. coli O157:H7

Genes Dev. 2000 Jul 15;14(14):1734-40.


Verotoxin II (VTII: or Shiga-like toxin 2) is a key factor for Escherichia coli O157:H7-induced multiple tissue failure and contains a pentameric sequence (NWGRI) similar to the Bcl-2 homolog domain, BH1. In the current study, we demonstrate that VTII, but not VTI, interacts with Bcl-2 through each BH1 domain pentameric sequence (NWGRI) and that the VTII/Bcl-2 complex is necessary for cell-death induction in target cells. VTII translocates to mitochondria and induces cell death only when target cells are expressing Bcl-2. In addition, interruption of VTII-Bcl-2 complex formation by a pentameric BH1 synthetic peptide suppresses VTII-induced cell death. In the present article, we propose that Bcl-2 mediates VTII-induced target cell death by the interaction with each pentameric sequence of BH1 domain.

MeSH terms

  • Amino Acid Sequence
  • Bacterial Toxins / chemistry
  • Bacterial Toxins / metabolism
  • Bacterial Toxins / toxicity*
  • Blotting, Western
  • Caspase 3
  • Caspases / metabolism
  • Cell Death*
  • Cell Nucleus / metabolism
  • Cell Survival / drug effects
  • DNA, Mitochondrial / metabolism
  • Dimerization
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Escherichia coli / metabolism
  • Humans
  • Microinjections
  • Mitochondria / metabolism
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Sequence Homology, Amino Acid
  • Shiga Toxin 1
  • Shiga Toxin 2
  • Time Factors
  • Transfection
  • Tumor Cells, Cultured


  • Bacterial Toxins
  • DNA, Mitochondrial
  • Proto-Oncogene Proteins c-bcl-2
  • Shiga Toxin 1
  • Shiga Toxin 2
  • CASP3 protein, human
  • Caspase 3
  • Caspases