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Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase
Article first published online: 25 DEC 2001
DOI: 10.1046/j.1365-2672.1999.00892.x
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How to Cite
Duesbery, N. S. and Woude, G. F. V. (1999), Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase. Journal of Applied Microbiology, 87: 289–293. doi: 10.1046/j.1365-2672.1999.00892.x
Publication History
- Issue published online: 25 DEC 2001
- Article first published online: 25 DEC 2001
- Received and revised 15 May 1999 and accepted 29 May 1999
- Abstract
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A search of the National Cancer Institute’s Anti-Neoplastic Drug Screen for compounds with an inhibitory profile similar to that of the mitogen-activated protein kinase kinase (MAPKK) inhibitor PD098059 yielded anthrax lethal toxin. Anthrax lethal factor was found to inhibit progesterone-induced meiotic maturation of frog oocytes by preventing the phosphorylation and activation of mitogen-activated protein kinase (MAPK). Similarly, lethal toxin prevented the activation of MAPK in serum stimulated, ras-transformed NIH3T3 cells. In vitro analyses using recombinant proteins indicated that lethal factor proteolytically modified the NH2-terminus of both MAPKK1 and 2, rendering them inactive and hence incapable of activating MAPK. The consequences of this inactivation upon meiosis and transformed cells are also discussed.