Journal ArticleDOI
Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor
Nicholas S. Duesbery,Craig P. Webb,Stephen H. Leppla,Valery M. Gordon,Kurt Klimpel,Terry D. Copeland,Natalie G. Ahn,M Oskarsson,Kenji Fukasawa,Ken D. Paull,George F. Vande Woude +10 more
TLDR
It is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway.Abstract:Â
Anthrax lethal toxin, produced by the bacterium Bacillus anthracis, is the major cause of death in animals infected with anthrax. One component of this toxin, lethal factor (LF), is suspected to be a metalloprotease, but no physiological substrates have been identified. Here it is shown that LF is a protease that cleaves the amino terminus of mitogen-activated protein kinase kinases 1 and 2 (MAPKK1 and MAPKK2) and that this cleavage inactivates MAPKK1 and inhibits the MAPK signal transduction pathway. The identification of a cleavage site for LF may facilitate the development of LF inhibitors.read more
Citations
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Journal ArticleDOI
Severe bacterial infections of the skin: uncommon presentations
TL;DR: The two life-threatening skin infections which are most commonly experienced are toxin-mediated staphylococcal and streptococcal disorders; one could overlap the other.
Book ChapterDOI
Virulence-Associated Mobile Elements in Bacilli and Clostridia
TL;DR: The extreme flexibility of the bacteria toward the loss and acquisition of virulence factors could help pathogenic bacteria adapt to the excessive pressure of selection to which they are subjected during the complex interactions between pathogens and their hosts.
Journal ArticleDOI
Anthrax prevention through vaccine and post-exposure therapy.
Manish Manish,Shashikala Verma,Divya Kandari,Parul Kulshreshtha,Samer Singh,Samer Singh,Rakesh Bhatnagar,Rakesh Bhatnagar +7 more
TL;DR: This work states that the identification of novel inhibitors targeting different key-molecules and vital-steps contributing to the overall anthrax pathophysiology could make a difference in anthrax control.
Journal ArticleDOI
The Disulfide Bond Cys255-Cys279 in the Immunoglobulin-Like Domain of Anthrax Toxin Receptor 2 Is Required for Membrane Insertion of Anthrax Protective Antigen Pore
Pedro Jacquez,Gustavo A. Avila,Kyle Boone,Agamyrat Altiyev,Jens Puschhof,Roland Sauter,Emma Arigi,Blanca Ruiz,Xiuli Peng,Igor C. Almeida,Michael B. Sherman,Chuan Xiao,Jianjun Sun +12 more
TL;DR: The biochemical and structural data obtained in this study provides a mechanistic insight into the role of the receptor disulfide bond C255-C279 in anthrax toxin action and may become a novel strategy to treat anthrax.
References
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A synthetic inhibitor of the mitogen-activated protein kinase cascade.
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Journal ArticleDOI
Cyclin is degraded by the ubiquitin pathway
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Journal ArticleDOI
Transformation of mammalian cells by constitutively active MAP kinase kinase
Sam J. Mansour,W. T. Matten,April S. Hermann,Julian M. Candia,Sing Rong,Kenji Fukasawa,G F Vande Woude,Natalie G. Ahn +7 more
TL;DR: It is found that constitutive activation of MAPKK is sufficient to promote cell transformation and is associated with highly tumorigenic in nude mice.
Journal ArticleDOI
Anthrax toxin edema factor: a bacterial adenylate cyclase that increases cyclic AMP concentrations of eukaryotic cells.
TL;DR: It is shown here that EF is an adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1] produced by Bacillus anthracis in an inactive form and nearly equals that of the most active known cyclase.
Journal ArticleDOI
Multiple Ras functions can contribute to mammalian cell transformation.
Michael A. White,Charles Nicolette,Audrey Minden,Anthony Polverino,Linda Van Aelst,Michael Karin,Michael Wigler +6 more
TL;DR: Results indicate that multiple cellular components, including Raf1, are activated by Ha-Ras and contribute to Ha- Ras-induced mammalian cell transformation.