Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/62046
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Type: Journal article
Title: Escherichia coli subtilase cytotoxin induces apoptosis regulated by host Bcl-2 family proteins Bax/Bak
Author: May, K.
Paton, J.
Paton, A.
Citation: Infection and Immunity, 2010; 78(11):4691-4696
Publisher: Amer Soc Microbiology
Issue Date: 2010
ISSN: 0019-9567
1098-5522
Statement of
Responsibility: 
Kerrie L. May, James C. Paton, and Adrienne W. Paton
Abstract: Subtilase cytotoxin (SubAB) was first isolated from a Shiga toxigenic Escherichia coli (STEC) strain that was responsible for an outbreak of hemolytic-uremic syndrome and is the prototype of a new family of AB5 cytotoxins. SubAB is a subtilase-like serine protease, and upon uptake by host cells, it is trafficked to the endoplasmic reticulum (ER), where it cleaves the essential ER chaperone BiP (GRP78) with high specificity. Previous work has shown that BiP cleavage by SubAB initiates ER stress-signaling pathways in host cells that eventuate in cell death associated with DNA fragmentation, a hallmark of apoptosis. The present study has investigated the role of the Bcl-2 protein family, which has been shown to regulate ER stress-induced apoptosis in other model systems. Examination of the cytotoxicity of SubAB for wild-type and bax–/–/bak–/– mouse embryonic fibroblasts and comparison of apoptotic markers in these cells revealed that SubAB cytotoxicity can be predominantly attributed to the activation of apoptotic pathways activated by Bax/Bak. The results of the present study further our understanding of the molecular mechanism whereby SubAB kills eukaryotic cells and contributes to STEC pathogenesis, in addition to consolidating the roles of Bcl-2 family members in the regulation of ER stress-induced apoptosis.
Keywords: Vero Cells; Endoplasmic Reticulum; Fibroblasts; Animals; Cercopithecus aethiops; Mice; Subtilisins; Escherichia coli Proteins; Apoptosis; DNA Fragmentation; Gene Expression Regulation; bcl-2 Homologous Antagonist-Killer Protein; bcl-2-Associated X Protein; Shiga-Toxigenic Escherichia coli
Rights: Copyright © 2010, American Society for Microbiology. All Rights Reserved.
RMID: 0020101159
DOI: 10.1128/IAI.00801-10
Appears in Collections:Molecular and Biomedical Science publications

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