Portal de Periódicos da CAPES

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

1999; Oxford University Press; Volume: 87; Issue: 2 Linguagem: Inglês

10.1046/j.1365-2672.1999.00892.x

1365-2672

Nicholas S. Duesbery, George F. Vande Woude,

Carcinogens and Genotoxicity Assessment

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.