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
Chapter 184 - X c,v Mammalian MAP Kinases
TL;DR: In this article, the properties of these MAP kinases and MAP kinase-related protein kinases are reviewed, including the dual-phosphorylation motifs that mediates MAP activation.
Book ChapterDOI
A Potent Non-Peptide Inhibitor of Anthrax Lethal Factor
Venkatachalapathi V. Yalamoori,M. G. de Luna,Darryl Rideout,Mark D. Shenderovich,Jian Hua Zheng,N. Duesberry,S. H. Leppla,Christina Niemeyer,J. Sun,Kalyanaraman Ramnarayan +9 more
TL;DR: The approach involves identifying small molecules that mimic the substrate MAPKK1 in the calculated MAPKK/LF complex, which differs from traditional rational drug design methods.
DissertationDOI
Design and Testing of Novel Anthrax Vaccines Utilizing a Tobacco Mosaic Virus Expression System
TL;DR: McComb et al. as mentioned in this paper presented a restricted to Claremont Colleges Dissertation for free and open access by the KGI Student Scholarship at Scholarship @ Claremont, which has been accepted for inclusion in KGI Theses and Dissertations by an authorized administrator.
References
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Journal ArticleDOI
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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.