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
RAS and the RAF/MEK/ERK Cascade
Deborah K. Morrison,Ira O. Daar +1 more
TL;DR: The Raf/MEK/ERK protein kinases constitute a key effector cascade used by Ras to relay signals regulating cell growth, survival, proliferation, and differentiation, allowing sensitive activation and deactivation of the pathway in response to diverse extracellular cues.
Journal ArticleDOI
Bismaleimide cross-linked anthrax toxin forms functional octamers with high specificity in tumor targeting.
Elyse S. Fischer,Warren A. Campbell,Shihui Liu,Rodolfo Ghirlando,Rasem J. Fattah,Thomas H. Bugge,Stephen H. Leppla +6 more
TL;DR: Overall, this work advances the development and use of the PA and LF tumor‐targeting system as a practical cancer therapeutic, as it provides a way to reduce the drug components of the anthrax toxin drug delivery system from three to two, which may lower the cost and simplify testing in clinical trials.
Journal ArticleDOI
Anthrax toxin channel: What we know based on over 30 years of research.
TL;DR: In this article, the authors focus on the biophysical studies of the anthrax toxin channel and compare it with the related clostridial binary toxin channels, and address issues linked to the toxin channel structural dynamics and lipid dependence.
Anthrax, Matrix Biology, and Angiogenesis: Capillary Morphogenesis Gene 2 Mediates Activity and Uptake of Type IV Collagen-Derived Anti-Angiogenic Peptides
TL;DR: Findings demonstrate that CMG2 is a functional receptor for Col IV NC1 domain fragments, and suggests a mechanism by whichCMG2 regulates ECM and basement membrane homeostasis, thereby establishing a functional connection between the receptor’s role in matrix biology and angiogenesis.
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.