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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DissertationDOI
Biochemische Charakterisierung einer Rezeptorvariante des Protektiven Antigens von Bacillus anthracis zur Entwicklung eines Makrophagen/Monozyten-selektiven Transporters
Increased Mitochondrial Activity in Anthrax-Induced Cell Death.
TL;DR: New work has demonstrated that increase of mitochondrial F1F0 ATPase activity and subsequent depletion of cellular ATP level are critical early events during LT-induced cell death.
Dissertation
Inflammasomes : des mécanismes d’activation de la caspase-1 à la progression tumorale
TL;DR: In this paper, the authors investigated the role of l'inflammasome in the progression of cancer and showed that the absence of caspase-1 and ASC can cause a reduction in the growth rate of cancer cells.
Journal ArticleDOI
A potent tumor-selective ERK pathway inactivator with high therapeutic index
Ze-Hua Zuo,Jie Liu,Zhihao Sun,R. Silverstein,Meijuan Zou,Toren Finkel,Thomas H. Bugge,Stephen H. Leppla,Shihui Liu +8 more
TL;DR: The reengineering of the anthrax toxin-based protein delivery system to develop a potent, tumor-selective MEK inactivator is demonstrated and it is suggested that engineered bacterial toxins can be modified to have significant in vitro and in vivo therapeutic effects with high therapeutic index.
Book ChapterDOI
CHAPTER 31 – Anthrax
TL;DR: Some of the most common findings in human inhalational anthrax concern the respiratory tract, andIntravenous ciprofloxacin or doxycycline is recommended for treatment of anthrax, usually as part of a cocktail of antibiotics.
References
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Journal ArticleDOI
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.
Journal ArticleDOI
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.