Sci. Signal., 15 June 2010
Lymphoma from Compromised ApoptosisThe four members of the nuclear Dbf2–related (NDR) family of serine and threonine protein kinases act in a number of cellular processes, including proliferation, cytokinesis, and apoptosis. Two family members, LATS1 and LATS2, act as tumor suppressor proteins in flies and mice. Of the other two, NDR1 is abundant in organs of the immune system, whereas NDR2 is predominantly found in the gastrointestinal tract. Cornils et al. found that mouse lymphocytes deficient in NDR1 compensated for this loss by increasing the abundance of NDR2 protein in a posttranscriptional manner. Blockade of this compensatory mechanism resulted in increased resistance of cells to various extrinsic and intrinsic proapoptotic stimuli. Aged NDR1+/– and NDR1–/– mice were more susceptible to the development of T cell lymphoma than were their wild-type counterparts, and this was associated with a loss in total NDR protein. Correlating with this finding, the abundance of NDR proteins was less in samples of human T cell lymphomas than in normal T cells, suggesting that NDR1 acts as a tumor suppressor protein.
Citation: H. Cornils, M. R. Stegert, A. Hergovich, D. Hynx, D. Schmitz, S. Dirnhofer, B. A. Hemmings, Ablation of the Kinase NDR1 Predisposes Mice to the Development of T Cell Lymphoma. Sci. Signal. 3, ra47 (2010).
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