Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor
10.1126/science.280.5364.734
Crossref journal-article
American Association for the Advancement of Science (AAAS)
Science (221)
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.

Bibliography

Duesbery, N. S., Webb, C. P., Leppla, S. H., Gordon, V. M., Klimpel, K. R., Copeland, T. D., Ahn, N. G., Oskarsson, M. K., Fukasawa, K., Paull, K. D., & Vande Woude, G. F. (1998). Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor. Science, 280(5364), 734–737.

Authors 11
  1. Nicholas S. Duesbery (first)
  2. Craig P. Webb (additional)
  3. Stephen H. Leppla (additional)
  4. Valery M. Gordon (additional)
  5. Kurt R. Klimpel (additional)
  6. Terry D. Copeland (additional)
  7. Natalie G. Ahn (additional)
  8. Marianne K. Oskarsson (additional)
  9. Kenji Fukasawa (additional)
  10. Ken D. Paull (additional)
  11. George F. Vande Woude (additional)
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  28. This paper is dedicated to the memory of Ken Paull whose untimely death is a significant loss to NCI and the cancer research community. The authors thank A. Cline and R. Frederickson for preparing the manuscript L. Miller for technical assistance H.-M. Koo for helpful discussions M. Jeffers and S. Koochekpour for critical comments on the manuscript and A. Murray for providing Δ90 cyclin. This research was sponsored in part by NCI Department of Health and Human Services under contract with Advanced BioScience Laboratories. By acceptance of this article the publisher or recipient acknowledges the right of the U.S. government and its contractors and agents to retain a nonexclusive royalty-free license in and to any copyright covering the article.
Dates
Type When
Created 23 years, 1 month ago (July 27, 2002, 5:35 a.m.)
Deposited 1 year, 7 months ago (Jan. 13, 2024, 12:16 a.m.)
Indexed 1 week, 3 days ago (Aug. 23, 2025, 12:59 a.m.)
Issued 27 years, 4 months ago (May 1, 1998)
Published 27 years, 4 months ago (May 1, 1998)
Published Print 27 years, 4 months ago (May 1, 1998)
Funders 0

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@article{Duesbery_1998, title={Proteolytic Inactivation of MAP-Kinase-Kinase by Anthrax Lethal Factor}, volume={280}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.280.5364.734}, DOI={10.1126/science.280.5364.734}, number={5364}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Duesbery, Nicholas S. and Webb, Craig P. and Leppla, Stephen H. and Gordon, Valery M. and Klimpel, Kurt R. and Copeland, Terry D. and Ahn, Natalie G. and Oskarsson, Marianne K. and Fukasawa, Kenji and Paull, Ken D. and Vande Woude, George F.}, year={1998}, month=may, pages={734–737} }