Mitogen-activated protein kinase kinase inhibition enhances nuclear proapoptotic function of p53 in acute myelogenous leukemia cells.

@article{Kojima2007MitogenactivatedPK,
  title={Mitogen-activated protein kinase kinase inhibition enhances nuclear proapoptotic function of p53 in acute myelogenous leukemia cells.},
  author={Kensuke Kojima and Marina Konopleva and Ismael J. Samudio and Vivian Ruvolo and Michael Andreeff},
  journal={Cancer research},
  year={2007},
  volume={67 7},
  pages={
          3210-9
        }
}
Activation of the Raf/MEK/ERK pathway and inactivation of wild-type p53 by Mdm2 overexpression are frequent molecular events in acute myelogenous leukemia (AML). We investigated the interaction of Raf/MEK/ERK and p53 pathways after their simultaneous blockades using a selective small-molecule antagonist of Mdm2, Nutlin-3a, and a pharmacologic MEK-specific inhibitor, PD98059. We found that PD98059, which itself has minimal apoptogenic activity, acts synergistically with Nutlin-3a to induce… CONTINUE READING
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