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Molecular and Cellular Biology, April 2004, p. 3404-3414, Vol. 24, No. 8
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.8.3404-3414.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Acetylation of ß-Catenin by p300 Regulates ß-Catenin-Tcf4 Interaction

Laurence Lévy,{dagger} Yu Wei, Charlotte Labalette, Yuanfei Wu, Claire-Angélique Renard, Marie Annick Buendia, and Christine Neuveut*

Unité d'Oncogenèse et Virologie Moléculaire (INSERM U579), Institut Pasteur, 75015 Paris, France

Received 24 July 2003/ Returned for modification 30 December 2003/ Accepted 16 January 2004

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 ß-catenin at lysine 345, located in arm repeat 6, in vitro and in vivo. Acetylation of this residue increased the affinity of ß-catenin for Tcf4, and the cellular Tcf4-bound pool of ß-catenin was significantly enriched in acetylated form. We demonstrated that the acetyltransferase activity of p300 was required for efficient activation of transcription mediated by ß-catenin/Tcf4 and that the cooperation between p300 and ß-catenin was severely reduced by the K345R mutation, implying that acetylation of ß-catenin plays a part in the coactivation of ß-catenin by p300. Interestingly, acetylation of ß-catenin had opposite, negative effects on the binding of ß-catenin to the androgen receptor. Our data suggest that acetylation of ß-catenin in the arm 6 domain regulates ß-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 ß-catenin transcriptional activity.

* Corresponding author. Mailing address: Unité d'Oncogenèse et Virologie Moléculaire (INSERM U579), Département de Virologie, Institut Pasteur, 28 Rue du Dr. Roux, 75724 Paris Cedex 15, France. Phone: 33-145 68 88 51. Fax: 33-145 68 89 43. E-mail: cneuveut{at}pasteur.fr.

{dagger} Present address: Laboratory of Developmental Signalling, Cancer Research United Kingdom London Research Institute, London WC2A 3PX, United Kingdom.

Molecular and Cellular Biology, April 2004, p. 3404-3414, Vol. 24, No. 8
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.8.3404-3414.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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