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Sci. Signal., 22 September 2009
Vol. 2, Issue 89, p. ra57
[DOI: 10.1126/scisignal.2000205]


MSK2 Inhibits p53 Activity in the Absence of Stress

Susana Llanos1*, Ana Cuadrado2, and Manuel Serrano1*

1 Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), 3 Melchor Fernandez Almagro Street, Madrid E-28029, Spain.
2 Signaling and Cell Cycle Group, Spanish National Cancer Research Centre (CNIO), Madrid E-28029, Spain.

Abstract: Mitogen- and stress-activated kinase 2 (MSK2) inhibits the transcription factor p53, and we investigate here the mechanisms underlying this inhibition. In the absence of stress stimuli, MSK2 selectively suppressed the expression of a subset of p53 target genes. This basal inhibition of p53 by MSK2 occurred independently of its kinase activity and of upstream mitogen-activated protein kinase signaling to MSK2. Furthermore, MSK2 interacted with and inhibited the p53 coactivator p300 and associated with the Noxa promoter. Apoptotic stimuli promoted the degradation of MSK2, thus relieving its inhibition of p53 and enabling efficient p53-dependent transactivation of Noxa, which contributed to apoptosis. Together, these findings constitute a new mechanism for the regulation of p53 transcriptional activity in response to stress.

* To whom correspondence should be addressed. E-mail: sllanos{at} (S.L.) and mserrano{at} (M.S.)

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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