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Cloned Shiga Toxin 2 B Subunit Induces Apoptosis in Ramos Burkitt's Lymphoma B Cells

2002· article· en· 29 citations· W4248032168 on OpenAlex· 10.1128/iai.70.3.1279-1286.2002

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Post-publication record

Nature
Retraction
Reason
Contamination of Materials;Error in Results and/or Conclusions;
Date
7/1/2003 0:00
Flagged by OpenAlex?
Yes

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Abstract

The Shiga toxins (Stx1 and Stx2), produced by Shigella dysenteriae type 1 and enterohemorrhagic Escherichia coli, consist of one A subunit and five B subunits. The Stx1 and Stx2 B subunits form a pentameric structure that binds to globotriaosylceramide (Gb3-Cer) receptors on eukaryotic cells and promotes endocytosis. The A subunit then inhibits protein biosynthesis, which triggers apoptosis in the affected cell. In addition to its Gb3-Cer binding activity, the data in the following report demonstrate that the Stx2 B pentamer induces apoptosis in Ramos Burkitt's lymphoma B cells independently of A subunit activity. Apoptosis was not observed in A subunit-free preparations of the Stx1 B pentamer which competitively inhibited Stx2 B pentamer-mediated apoptosis. The pancaspase inhibitor, Z-VAD-fmk, prevented apoptosis in Ramos cells exposed to the Stx2 B subunit, Stx1 or Stx2. Brefeldin A, an inhibitor of the Golgi transport system, also prevented Stx2 B subunit-mediated apoptosis. These observations suggest that the Stx2 B subunit must be internalized, via Gb3-Cer receptors, to induce Ramos cell apoptosis. Moreover, unlike the two holotoxins, Stx2 B subunit-mediated apoptosis does not involve inhibition of protein biosynthesis. This study provides further insight into the pathogenic potential of this family of potent bacterial exotoxins.

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The record

Venue
Infection and Immunity
Topic
Escherichia coli research studies
Field
Biochemistry, Genetics and Molecular Biology
Canadian institutions
University of Alberta
Funders
H2020 European Research Council
Keywords
Shiga toxinBiologyPentamerApoptosisProtein subunitMolecular biologyShigella dysenteriaeCell biologyBiochemistryEscherichia coli
Has abstract in OpenAlex
yes