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
Signal transduction by the JNK group of MAP kinases.
TL;DR: This review will focus on the JNK group of MAP kinases, which are characterized by the sequence TEY and the two stress-activatedMAP kinases: p38 with the sequence TGY, and the c-Jun NH2-terminal kinases (JNK) with the sequences TPY.
Journal ArticleDOI
Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions.
Gray W. Pearson,Fred L. Robinson,Tara Beers Gibson,Bing E. Xu,Mahesh Karandikar,Kevin S. Berman,Melanie H. Cobb +6 more
TL;DR: Nonenzymatic mechanisms that impact MAP kinase functions and findings from gene disruption studies are highlighted and particular emphasis is on ERK1/2.
Journal ArticleDOI
The NCI60 human tumour cell line anticancer drug screen
TL;DR: The development, use and productivity of the NCI60 screen are reviewed, highlighting several outcomes that have contributed to advances in cancer chemotherapy.
Journal ArticleDOI
Targeting virulence: a new paradigm for antimicrobial therapy
TL;DR: It is proposed that in addition to targeting virulence, new antimicrobial development strategies should be expanded to include targeting bacterial gene functions that are essential for in vivo viability.
Journal ArticleDOI
Jasmonate and salicylate as global signals for defense gene expression
TL;DR: Only a few low molecular mass signals, including jasmonic acid, ethylene and salicylic acid, upregulate the expression of scores of defense-related genes, which fine-tunes its defense gene expression against aggressors.
References
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Journal ArticleDOI
The cytotoxic activity of Bacillus anthracis lethal factor is inhibited by leukotriene A4 hydrolase and metallopeptidase inhibitors.
TL;DR: Results support the proposal that anthrax lethal factor might display in the cytosol of intoxicated cells a peptidase activity similar to that of LTA4 hydrolase, a bifunctional enzyme also endowed with a metallopeptid enzyme activity.
Book ChapterDOI
Mechanisms of Xenopus oocyte maturation
M. S. Murakami,G. F. Vande Woude +1 more
TL;DR: This chapter discusses the mechanisms of xenopus oocyte maturation, which consists of entry into and completion of meiosis I, entry into meiosis II, and arrest at metaphase of meiotic II.