Rolando, MStefani, CFlatau, GAuberger, PMettouchi, AMhlanga, MusaRapp, UGalmiche, ALemichez, E2010-11-112010-11-112010-07Rolando, 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 891-9051462-5814http://onlinelibrary.wiley.com/doi/10.1111/j.1462-5822.2010.01438.x/pdfhttp://hdl.handle.net/10204/4551Copyright: 2010 Wiley Blackwell. This is the post print version of the work. The definitive version is published in Cellular Microbiology, Vol. 12(7), pp 891-905The 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.enLethal toxinAnthraxHuman endothelial cellCell toxicityBacillus anthracisCellular microbiologyTranscriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicityArticleRolando, M., Stefani, C., Flatau, G., Auberger, P., Mettouchi, A., Mhlanga, M., ... Lemichez, E. (2010). Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity. http://hdl.handle.net/10204/4551Rolando, M, C Stefani, G Flatau, P Auberger, A Mettouchi, Musa Mhlanga, U Rapp, A Galmiche, and E Lemichez "Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity." (2010) http://hdl.handle.net/10204/4551Rolando M, Stefani C, Flatau G, Auberger P, Mettouchi A, Mhlanga M, et al. Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity. 2010; http://hdl.handle.net/10204/4551.TY - Article AU - Rolando, M AU - Stefani, C AU - Flatau, G AU - Auberger, P AU - Mettouchi, A AU - Mhlanga, Musa AU - Rapp, U AU - Galmiche, A AU - Lemichez, E AB - 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. DA - 2010-07 DB - ResearchSpace DP - CSIR KW - Lethal toxin KW - Anthrax KW - Human endothelial cell KW - Cell toxicity KW - Bacillus anthracis KW - Cellular microbiology LK - https://researchspace.csir.co.za PY - 2010 SM - 1462-5814 T1 - Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity TI - Transcriptome dysregulation by anthrax lethal toxin plays a key role in induction of human endothelial cell cytotoxicity UR - http://hdl.handle.net/10204/4551 ER -