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

  1. Author:
    Duesbery, N. S.
    Vande Woude, G. F.

  2. Author Address

    Vande Woude GF NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci POB B Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, Div Basic Sci Frederick, MD 21702 USA NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program Frederick, MD 21702 USA
    1. Year: 1999
  2. Journal: Journal of Applied Microbiology
    1. 87
    2. 2
    3. Pages: 289-293
  4. Type of Article: Article
  1. 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 tor;in 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. [References: 32]

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