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Please use this identifier to cite or link to this item: http://hdl.handle.net/10204/4551

Title: Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity
Authors: Rolando, M
Stefani, C
Flatau, G
Auberger, P
Mettouchi, A
Mhlanga, M
Rapp, U
Galmiche, A
Lemichez, E
Keywords: Lethal toxin
Anthrax
Human endothelial cell
Cell toxicity
Bacillus anthracis
Cellular microbiology
Issue Date: Jul-2010
Publisher: Wiley-Blackwell
Citation: Rolando, M, Stefani, C, Flatau, G et al. 2010. Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity. Cellular Microbiology, Vol. 12(7), pp 891-905
Series/Report no.: Journal Article
Abstract: The authors have investigated how Bacillus anthracis lethal toxin (LT) triggers caspase-3 activation and the formation of thick actin cables in human endothelial cells. By DNA array analysis they show that LT has a major impact on the cell transcriptome and they identify key host genes involved in LT cytotoxic effects. Indeed, upregulation of TRAIL and downregulation of XIAP both participate in LT-induced caspase-3 activation. LT induces a downregulation of the immediate early gene and master regulator of transcription egr1. Importantly, its re-expression in LT-intoxicated cells blocks caspase-3 activation. In parallel, they found that the formation of actin cables induced by LT occurs in the absence of direct activation of RhoA/ROCK signalling. They show that knock-down of cortactin and rhophilin-2 under conditions of calponin-1 expression defines the minimal set of genes regulated by LT for actin cable formation. Together their data establish that the modulation of the cell transcriptome by LT plays a key role in triggering human endothelial cell toxicity.
Description: Copyright: 2010 Wiley Blackwell. This is the post print version of the work. The definitive version is published in Cellular Microbiology, Vol. 12(7), pp 891-905
URI: http://onlinelibrary.wiley.com/doi/10.1111/j.1462-5822.2010.01438.x/pdf
http://hdl.handle.net/10204/4551
ISSN: 1462-5814
Appears in Collections:Resource-based sustainable development
Nanotechnology
Microbial expression systems
General science, engineering & technology
Bioprospecting

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