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:
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
Killed but Metabolically Active Bacillus anthracis Vaccines Induce Broad and Protective Immunity against Anthrax
Justin Skoble,John W. Beaber,Yi Gao,Julie A. Lovchik,Laurie E. Sower,Weiqun Liu,William S. Luckett,Johnny W. Peterson,Richard Calendar,Daniel A. Portnoy,C. Rick Lyons,Thomas W. Dubensky +11 more
TL;DR: Data demonstrate that KBMA anthrax vaccines are well tolerated and elicit potent protective immune responses, and the use of KBMA vaccines may be broadly applicable to bacterial pathogens, especially those for which the correlates of protective immunity are unknown.
Journal ArticleDOI
Protection of mice against challenge with Bacillus anthracis STI spores after DNA vaccination
TL;DR: Genetic vaccination with plasmid vectors encoding PA showed significant protection of A/J mice against infection with B. anthracis STI spores, and induced PA-specific humoral immune responses, predominantly IgG1 antibodies, in mice.
Journal ArticleDOI
Recombinant Anthrax Toxin Receptor-Fc Fusion Proteins Produced in Plants Protect Rabbits against Inhalational Anthrax
Keith L. Wycoff,Archana Belle,Dorothée Deppe,Leah Schaefer,James Maclean,Simone Haase,Anke K. Trilling,Shihui Liu,Stephen H. Leppla,Isin N. Geren,Isin N. Geren,Jennifer Pawlik,Johnny W. Peterson +12 more
TL;DR: A fusion of the extracellular domain of human CMG2 and human IgG Fc effectively neutralized, in vitro, LeTx-containing mutant forms of PA that were not neutralized by anti-PA monoclonal antibodies.
Journal ArticleDOI
Anthrax toxin receptor 2 determinants that dictate the pH threshold of toxin pore formation.
Heather M. Scobie,Heather M. Scobie,John M. Marlett,G. Jonah A. Rainey,D. Borden Lacy,R. John Collier,John A. Young +6 more
TL;DR: Genetic evidence for receptor release of these regions of PA as being necessary for the protein rearrangements that accompany anthrax toxin pore formation is provided.
Journal ArticleDOI
Anthrax SET protein: a potential virulence determinant that epigenetically represses NF-κB activation in infected macrophages
Shiraz Mujtaba,Benjamin Y. Winer,Anbalagan Jaganathan,Jigneshkumar Patel,Miriam Sgobba,Raymond Schuch,Yogesh K. Gupta,Shozeb Haider,Rong Wang,Vincent A. Fischetti +9 more
TL;DR: BaSET methylates human histone H1, resulting in repression of NF-κB functions, which is required for repression of host transcription as well as proper B. anthracis growth, making it a potentially unique virulence determinant.
References
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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
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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.