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https://hdl.handle.net/2440/51569
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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 1462-5822 |
Statement of Responsibility: | 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 eIF-2 Kinase Escherichia coli Proteins Signal Transduction Activating Transcription Factor 6 Shiga-Toxigenic Escherichia coli Chlorocebus aethiops Protein Serine-Threonine Kinases |
Description: | © 2008 Blackwell Publishing Ltd |
DOI: | 10.1111/j.1462-5822.2008.01164.x |
Published version: | http://dx.doi.org/10.1111/j.1462-5822.2008.01164.x |
Appears in Collections: | Aurora harvest Molecular and Biomedical Science publications |
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