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
Suppression of ras-mediated transformation and inhibition of tumor growth and angiogenesis by anthrax lethal factor, a proteolytic inhibitor of multiple MEK pathways.
Nicholas S. Duesbery,James H. Resau,Craig P. Webb,Shahriar Koochekpour,Han-Mo Koo,Stephen H. Leppla,G F Vande Woude +6 more
TL;DR: It is demonstrated that LeTx potently inhibits ras-mediated tumor growth and is a potential antitumor therapeutic.
Journal ArticleDOI
Proteolytic activation of receptor-bound anthrax protective antigen on macrophages promotes its internalization
TL;DR: The studies show that proteolytic cleavage of PA, in addition to permitting oligomerization and LF binding, also promotes internalization of the protein.
Journal ArticleDOI
Clostridium difficile virulence factors: Insights into an anaerobic spore-forming pathogen.
TL;DR: The worldwide emergence of epidemic strains of Clostridium difficile linked to increased disease severity and mortality has resulted in greater research efforts toward determining the virulence factors and pathogenesis mechanisms used by this organism to cause disease.
Journal ArticleDOI
A peptide-based fluorescence resonance energy transfer assay for Bacillus anthracis lethal factor protease
Richard T. Cummings,Scott P. Salowe,Barry R. Cunningham,Judyann Wiltsie,Young Whan Park,Lisa M. Sonatore,Douglas Wisniewski,Cameron M. Douglas,Jeffrey D. Hermes,Edward M. Scolnick +9 more
TL;DR: Extension of this work to a fluorogenic 19-mer peptide, derived, in part, from a consensus sequence of known LF protease targets, produced a much better substrate, cleaving approximately 100 times more efficiently.
Journal ArticleDOI
Bacillus anthracis: toxicology, epidemiology and current rapid-detection methods.
TL;DR: A brief background on the toxicology and epidemiology of B. anthracis is provided, challenges associated with its detection related to genetic similarities to other species are discussed, and immunological and, with greater emphasis, nucleic acid-based detection systems are reviewed.
References
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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.