Subtilase cytotoxin activates PERK, IRE1 and ATF6 endoplasmic reticulum stress-signalling pathways
Open Access
- 5 August 2008
- journal article
- Published by Hindawi Limited in Cellular Microbiology
- Vol. 10 (9), 1775-1786
- https://doi.org/10.1111/j.1462-5822.2008.01164.x
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
This publication has 26 references indexed in Scilit:
- West Nile Virus Infection Activates the Unfolded Protein Response, Leading to CHOP Induction and ApoptosisJournal of Virology, 2007
- Pathologic Changes in Mice Induced by Subtilase Cytotoxin, a Potent NewEscherichia coliAB5Toxin That Targets the Endoplasmic ReticulumThe Journal of Infectious Diseases, 2007
- Mediators of endoplasmic reticulum stress‐induced apoptosisEMBO Reports, 2006
- Intrinsic Capacities of Molecular Sensors of the Unfolded Protein Response to Sense Alternate Forms of Endoplasmic Reticulum StressMolecular Biology of the Cell, 2006
- Autocrine Tumor Necrosis Factor Alpha Links Endoplasmic Reticulum Stress to the Membrane Death Receptor Pathway through IRE1α-Mediated NF-κB Activation and Down-Regulation of TRAF2 ExpressionMolecular and Cellular Biology, 2006
- Cellular response to endoplasmic reticulum stress: a matter of life or deathCell Death & Differentiation, 2006
- Hepatitis C virus envelope proteins regulate CHOP via induction of the unfolded protein responseThe FASEB Journal, 2005
- Quantitative measurement of events in the mammalian unfolded protein responseMethods, 2005
- Overexpression of endoplasmic reticulum molecular chaperone GRP94 and GRP78 in human lung cancer tissues and its significanceCancer Detection Prevention, 2005
- Subtilases: The superfamily of subtilisin-like serine proteasesProtein Science, 1997