Acetylation of beta-catenin by p300 regulates beta-catenin-Tcf4 interaction.

Unité d'Oncogenèse et Virologie Moléculaire (INSERM U579), Institut Pasteur, 75015 Paris, France.
Molecular and Cellular Biology (Impact Factor: 5.04). 05/2004; 24(8):3404-14. DOI: 10.1128/MCB.24.8.3404-3414.2004
Source: PubMed

ABSTRACT Lysine acetylation modulates the activities of nonhistone regulatory proteins and plays a critical role in the regulation of cellular gene transcription. In this study, we showed that the transcriptional coactivator p300 acetylated beta-catenin at lysine 345, located in arm repeat 6, in vitro and in vivo. Acetylation of this residue increased the affinity of beta-catenin for Tcf4, and the cellular Tcf4-bound pool of beta-catenin was significantly enriched in acetylated form. We demonstrated that the acetyltransferase activity of p300 was required for efficient activation of transcription mediated by beta-catenin/Tcf4 and that the cooperation between p300 and beta-catenin was severely reduced by the K345R mutation, implying that acetylation of beta-catenin plays a part in the coactivation of beta-catenin by p300. Interestingly, acetylation of beta-catenin had opposite, negative effects on the binding of beta-catenin to the androgen receptor. Our data suggest that acetylation of beta-catenin in the arm 6 domain regulates beta-catenin transcriptional activity by differentially modulating its affinity for Tcf4 and the androgen receptor. Thus, our results describe a new mechanism by which p300 might regulate beta-catenin transcriptional activity.

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Available from: Marie-Annick Buendia, Jun 18, 2015
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