Anthrax lethal factor causes proteolytic inactivation of mitogen-activated protein kinase kinase

Authors: Duesbery, N. S.¹; Woude, G. F. Vande²

Source: Journal of Applied Microbiology, Volume 87, Number 2, August 1999 , pp. 289-293(5)

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Abstract:

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.

Document Type: Research article

DOI: http://dx.doi.org/10.1046/j.1365-2672.1999.00892.x

Affiliations: 1: ABL-Basic Research Program, and 2: National Cancer Institute, Division of Basic Sciences, NCI-FCRDC, Frederick, MD, USA

Publication date: 1999-08-01