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Type: Journal article
Title: Subtilase cytotoxin activates PERK, IRE1 and ATF6 endoplasmic reticulum stress-signalling pathways
Author: Wolfson, J.
May, K.
Thorpe, C.
Jandhyala, D.
Paton, J.
Paton, A.
Citation: Cellular Microbiology, 2008; 10(9):1775-1786
Publisher: Blackwell Science Ltd
Issue Date: 2008
ISSN: 1462-5814
Statement of
Jennifer J. Wolfson, Kerrie L. May, Cheleste M. Thorpe, Dakshina M. Jandhyala, James C. Paton and Adrienne W. Paton
Abstract: Subtilase cytotoxin (SubAB) is the prototype of a new family of AB5 cytotoxins produced by Shiga toxigenic Escherichia coli. Its cytotoxic activity is due to its capacity to enter cells and specifically cleave the essential endoplasmic reticulum (ER) chaperone BiP (GRP78). In the present study, we have examined its capacity to trigger the three ER stress-signalling pathways in Vero cells. Activation of PKR-like ER kinase was demonstrated by phosphorylation of eIF2α, which occurred within 30 min of toxin treatment, and correlated with inhibition of global protein synthesis. Activation of inositol-requiring enzyme 1 was demonstrated by splicing of X-box-binding protein 1 mRNA, while activating transcription factor 6 activation was demonstrated by depletion of the 90 kDa uncleaved form, and appearance of the 50 kDa cleaved form. The rapidity with which ER stress-signalling responses are triggered by exposure of cells to SubAB is consistent with the hypothesis that cleavage by the toxin causes BiP to dissociate from the signalling molecules.
Keywords: Vero Cells; Endoplasmic Reticulum; Animals; Subtilisins; Protein-Serine-Threonine Kinases; eIF-2 Kinase; Escherichia coli Proteins; Signal Transduction; Activating Transcription Factor 6; Shiga-Toxigenic Escherichia coli; Chlorocebus aethiops
Description: © 2008 Blackwell Publishing Ltd
RMID: 0020081993
DOI: 10.1111/j.1462-5822.2008.01164.x
Appears in Collections:Molecular and Biomedical Science publications

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