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
Anthrax toxin protective antigen—Insights into molecular switching from prepore to pore
TL;DR: A model is proposed for the kinetic steps for protective antigen conversion from prepore to pore, and the driving force for pore formation is the formation of the phi (ϕ)‐clamp, a region that forms a leak‐free seal around the translocating polypeptide.
Journal ArticleDOI
MEK Wars, a new front in the battle against cancer
TL;DR: A specific inhibitor of the mitogen-activated protein kinase (MAPK or ERK) pathway is introduced as a new member in the growing search for cytostatic drugs that block tumor growth.
Journal ArticleDOI
Regulation of Apoptosis by Gram-Positive Bacteria: Mechanistic Diversity and Consequences for Immunity
TL;DR: Bacterial virulence factors, which represent the keys to unlocking the suicide response in host cells, are a primary focus of this field and are discussed as important agents of human infection that modulate PCD pathways in eukaryotic cells.
Journal ArticleDOI
Anti-toxin antibodies in prophylaxis and treatment of inhalation anthrax.
TL;DR: Since 2001, significant progress has been made in isolation and commercial development of monoclonal and polyclonal antibodies that function as potent neutralizers of anthrax lethal toxin in both a prophylactic and therapeutic setting.
Journal ArticleDOI
Xp38γ/SAPK3 promotes meiotic G2/M transition in Xenopus oocytes and activates Cdc25C
Eusebio Perdiguero,Marie-Jeanne Pillaire,Jean-François Bodart,Florian Hennersdorf,Morten Frödin,Nicholas S. Duesbery,Gema Alonso,Angel R. Nebreda +7 more
TL;DR: It is shown that MKK6 can rescue the inhibition of oocyte maturation by anthrax lethal factor, a protease that inactivates MAPK kinases, and phosphorylation of XCdc25C by Xp38γ/SAPK3 is important for the meiotic G2/M progression of Xenopus oocytes.
References
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A synthetic inhibitor of the mitogen-activated protein kinase cascade.
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Cyclin is degraded by the ubiquitin pathway
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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.
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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.