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Sci. Signal., 22 September 2009
Vol. 2, Issue 89, p. ra57
Kinase Activity Not Required
The tumor suppressor p53, which mediates transcriptional responses to DNA damage, is encoded by one of the genes most frequently mutated in cancer cells. Its activity can be regulated by various binding partners, including the mitogen- and stress-activated kinase 2 (MSK2). Although MSK2 regulates the activity of other transcription factors through phosphorylation, Llanos et al. show that inhibition of p53 by MSK2 does not require its catalytic activity. p53 transcriptional activity was inhibited by an MSK2 mutant that lacked both of its kinase domains. MSK2 inhibited basal p53 activity at select promoters by reducing the activity of the histone deacetylase p300, which coactivates p53. Specific apoptotic stimuli led to MSK2 degradation, enabling p53-mediated induction of the pro-apoptotic protein Noxa. Thus, these results delineate a kinase-independent function for MSK2 and a new pathway whereby the activity of p53 can be regulated.
Citation: S. Llanos, A. Cuadrado, M. Serrano, MSK2 Inhibits p53 Activity in the Absence of Stress. Sci. Signal.2, ra57 (2009).
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