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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Book ChapterDOI
15 Membrane translocation by bacterial AB toxins
TL;DR: The technologies described in this chapter have been used to identify the mechanisms of internalization and intracellular compartments from which AB-toxins gain entry to the cytosol.
Journal ArticleDOI
Feasibility of the use of ELISA in an immunogenicity-based potency test of anthrax vaccines.
TL;DR: In additional immunogenicity experiments neither the magnitude of the response to a single dose of vaccine, nor the estimation of the dose necessary to induce a measurable response were able to consistently detect brief exposure of vaccines to potentially damaging temperatures.
Journal ArticleDOI
Molecular dynamics simulations of complexes between wild-type and mutant anthrax protective antigen variants and a model anthrax toxin receptor.
Linsey Stiles,Donald J. Nelson +1 more
TL;DR: The results of 1,000 psec molecular dynamics simulations carried out on complexes between the Anthrax Protective Antigen Domain 4 (PA-D4) and the von Willebrand Factor A (VWA/I) indicate the importance of the mutated PA-D 4 residues in both the “small loop” and at the carboxyl terminus in maintaining a PA conformation that is capable of effective interaction with the anthrax toxin receptor.
Journal ArticleDOI
[Molecular model of anthrax toxin translocation into target-cells]
TL;DR: Molecular mechanism of receptor-mediated endocytosis for binary toxins is proposed in this publication and effector oligomeric complex with common structure 7A + 7B* (but not separated A subunits) penetrates into target cells.
Dissertation
Structural and stability studies on domain IV of anthrax toxin protective antigen (PA); its role in anthrax pathogenesis
TL;DR: Thesis (Ph.D.) as mentioned in this paper, Wichita State University, College of Liberal Arts and Sciences, Dept. of Chemistry (CLAS), WSU, Wichita, KS.
References
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A synthetic inhibitor of the mitogen-activated protein kinase cascade.
TL;DR: Results indicate that the MAPK pathway is essential for growth and maintenance of the ras-transformed phenotype and PD 098059 is an invaluable tool that will help elucidate the role of theMAPK cascade in a variety of biological settings.
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Cyclin is degraded by the ubiquitin pathway
TL;DR: Cyclin degradation is the key step governing exit from mitosis and progress into the next cell cycle, and anaphase may be triggered by the recognition of cyclin by the ubiquitin-conjugating system.
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.