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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Identification, Functional Characterization, and Regulon Prediction of the Zinc Uptake Regulator (zur) of Bacillus anthracis - An Insight Into the Zinc Homeostasis of the Pathogen.
TL;DR: This study functionally characterizes Zur of B. anthracis and elucidates its role in maintaining zinc homeostasis and an increase in the transcript levels of the regulon genes znuA, rpmG, and yciC upon exposure of cells to TPEN connoted their role in combating hypo-zincemic conditions by bringing about zinc uptake and mobilization.
Patent
Modified MEK1 and MEK2, crystal of a peptide: ligand: cofactor complex containing such modified MEK1 or MEK2, and methods of use thereof
Jeffrey F. Ohren,Huifen Chen,Amy Marie Delaney,David T. Dudley,Charles A. Hasemann,Peter Kuffa,Patrick Charles Mcconnell,Alexander Pavlovsky,Haile Tecle,Christopher Whitehead,Chunhong Yan,Erli Zhang +11 more
TL;DR: In this paper, the three-dimensional structures of MEK1 and MEK2 peptides, including the cofactor and ligand-binding pockets, have been discovered, and uses of this information, for example, in molecular replacement and the modification, design and screening of compounds that may associate with MEK 1, MEK 2 or peptides structurally related thereto, have also been discovered.
Journal ArticleDOI
Detection of protective antigen, an anthrax specific toxin in human serum by using surface plasmon resonance
TL;DR: In this paper, surface plasmon resonance (SPR) technology was used for the sensitive detection of protective antigen (PA), an anthrax specific toxin in spiked human serum samples.
Journal ArticleDOI
Regulation of the G2/M transition in oocytes of xenopus tropicalis.
TL;DR: This work finds that injection of egg cytoplasm ("MPF activity") into G2-arrested X. tropicalis oocytes induces entry into meiosis I even when protein synthesis is blocked, just as it does in oocytes of X. laevis, and suggests that X. Tropicalis Oocytes offer a good experimental system for investigating certain questions that require a rapid, synchronous progression through the G2/meiosis I transition.
Journal ArticleDOI
Bacterial toxins and the immune system: show me the in vivo targets
TL;DR: A large number of bacterial toxins have been shown in vitro to disrupt immune cell functions and whether these toxins have specifically evolved to disrupt the adaptive immune system is unclear.
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.