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Literature summary for 3.4.24.83 extracted from

  • Raymond, B.; Batsche, E.; Boutillon, F.; Wu, Y.Z.; Leduc, D.; Balloy, V.; Raoust, E.; Muchardt, C.; Goossens, P.L.; Touqui, L.
    Anthrax lethal toxin impairs IL-8 expression in epithelial cells through inhibition of histone H3 modification (2009), PLoS Pathog., 5, e1000359.
    View publication on PubMedView publication on EuropePMC

Application

Application Comment Organism
molecular biology Bacillus anthracis represses the immune response, in part by altering chromatin accessibility of IL-8 promoter to NFkappaB in epithelial cells. This epigenetic reprogramming, in addition to previously reported effects of lethal toxin, represents an efficient strategy used by Bacillus anthracis for invading the host Bacillus anthracis

Protein Variants

Protein Variants Comment Organism
additional information intranasal instillationin a mouse model of pulmonary anthrax of a Bacillus anthracis strain RPLC2 bearing inactive lethal toxin (double mutant) lethal toxin stimulates cytokine production (IL-6 and KC, mouse orthologue of IL-8) and polymorphonuclear neutrophils recruitment in lungs. These responses are repressed by a prior instillation of an lethal toxin preparation. In contrast, instillation of a Bacillus anthracis strain expressing active lethal toxin represses lung inflammation. The inhibitory effects of lethal toxin on cytokine production are associated with an alteration of ERK and p38-MAPK phosphorylation, but not JNK phosphorylation. Although NF-kappaB is essential for IL-8 expression, lethal toxin downregulates this expression without interfering with NF-kappaB activation in epithelial cells. Lethal toxin selectively prevents histone H3 phosphorylation at Ser 10 and recruitment of the p65 subunit of NF-kappaB at the IL-8 and KC promoters Bacillus anthracis

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
additional information Bacillus anthracis prevention of inflammatory response of immune system by preventing interleukin-8 expression: selective blocking of histone H3 phosphorylation at serine 10 and acetylation at lysine 14, H3 normally promotes the accessibility of NF-kappaB (transcription factor for inflammatory gene expression) to target promoters, the histone blocking is mitigated by cleaving mitogen-activated protein kinase kinase, thus preventing the activation of p38-mitogen-activated protein kinase and extracellular signal-regulated kinase ?
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Organism

Organism UniProt Comment Textmining
Bacillus anthracis
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Bacillus anthracis
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single mutant strain RP9 producing active lethal factor and inactive edema factor, and double-mutant strain RPLC2 producing inactive lethal factor and edema factor, action in mouse model and in human epithelial lung cells
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Source Tissue

Source Tissue Comment Organism Textmining

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information prevention of inflammatory response of immune system by preventing interleukin-8 expression: selective blocking of histone H3 phosphorylation at serine 10 and acetylation at lysine 14, H3 normally promotes the accessibility of NF-kappaB (transcription factor for inflammatory gene expression) to target promoters, the histone blocking is mitigated by cleaving mitogen-activated protein kinase kinase, thus preventing the activation of p38-mitogen-activated protein kinase and extracellular signal-regulated kinase Bacillus anthracis ?
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Synonyms

Synonyms Comment Organism
anthrax lethal toxin
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Bacillus anthracis
anthrax lethal toxin LT Bacillus anthracis