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
Soluble Expression and Characterization of Biologically Active Bacillus anthracis Protective Antigen in Escherichia coli
Nagendra Suryanarayana,Vanlalhmuaka,Bharti Mankere,Monika Verma,Kulanthaivel Thavachelvam,Urmil Tuteja +5 more
TL;DR: The expression of soluble and biologically active recombinant PA in larger quantity using simpler E. coli production platform is highlighted.
Journal ArticleDOI
Identification of new dominant-negative mutants of anthrax protective antigen using directed evolution.
TL;DR: A PA mutant library was constructed by introducing random mutations into domain II of PA and screened three new DN mutants of PA that inhibited the anthrax toxin action against sensitive cells and were confirmed to be able to protect mice against a challenge with anthrax lethal toxin.
Journal ArticleDOI
Inhibitory Effects of a Reengineered Anthrax Toxin on Canine Oral Mucosal Melanomas.
Adriana Tomoko Nishiya,Márcia Kazumi Nagamine,Ivone Izabel Mackowiak da Fonseca,Andrea Caringi Miraldo,Nayra Villar Scattone,José Luiz Guerra,José Guilherme Xavier,Mário Santos,Cristina Oliveira Massoco de Salles Gomes,Jerrold M. Ward,Shihui Liu,Stephen H. Leppla,Thomas H. Bugge,Maria Lúcia Zaidan Dagli +13 more
TL;DR: The reengineered anthrax toxin exerted inhibitory effects when administered intratumorally, and systemic administration of this toxin is a promising therapy for canine OMM.
Patent
Lyophilized formulations of salinosporamide a
Barbara C. M. Potts,Ramsharan Singh,Jan-Jon Chu,Bao Viet Mai,Natasha Reddinger,Cheryl (Billstrom) Sifferlen +5 more
TL;DR: In this article, the authors present methods of lyophilizing Salinosporamide A or analogs thereof using a solvent or co-solvent system, and they also provide methods of administering SALINO-PORAMA A or analogues thereof to patients.
Journal ArticleDOI
Anthrax lethal toxin rapidly reduces c-Jun levels by inhibiting c-Jun gene transcription and promoting c-Jun protein degradation.
TL;DR: It is reported that LT exposure rapidly reduces the levels of c-Jun, a key regulator of cell proliferation and survival, and inhibited cell proliferation, thereby inhibiting critical cell functions, including cellular proliferation.
References
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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
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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.