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

Unité d'Oncogenèse et Virologie Moléculaire (INSERM U579), Institut Pasteur, 75015 Paris, France.
Molecular and Cellular Biology (Impact Factor: 4.78). 05/2004; 24(8):3404-14. DOI: 10.1128/MCB.24.8.3404-3414.2004
Source: PubMed


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

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