Bcl-2 antiapoptotic protein mediates verotoxin II-induced cell death: possible association between bcl-2 and tissue failure by E. coli O157:H7.
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.
Suzuki
A
A
Project for the Cell Death Research, Basic Technology Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo R&D Center, Tokyo 134-8630, Japan. leb00373@nifty.ne.jp
Doi
H
H
Matsuzawa
F
F
Aikawa
S
S
Takiguchi
K
K
Kawano
H
H
Hayashida
M
M
Ohno
S
S
D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004272:DNA, Mitochondrial / Q000378:metabolism; D019281:Dimerization; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D008845:Microinjections; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism* / Q000502:physiology*; D017386:Sequence Homology, Amino Acid; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D001427:Bacterial Toxins; D004272:DNA, Mitochondrial; D019253:Proto-Oncogene Proteins c-bcl-2; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases