Acetylation of beta-catenin by p300 regulates beta-catenin-Tcf4 interaction.
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.
Mesh Terms:
Acetylation, Acetyltransferases, Amino Acid Sequence, Cell Cycle Proteins, Cell Line, Cytoskeletal Proteins, DNA-Binding Proteins, Genes, Reporter, Histone Acetyltransferases, Humans, Lysine, Molecular Sequence Data, Peptides, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Recombinant Fusion Proteins, TCF Transcription Factors, Trans-Activators, Transcription Factor 7-Like 2 Protein, Transcription Factors, Transcription, Genetic, Wnt Proteins, Zebrafish Proteins, beta Catenin, p300-CBP Transcription Factors
Acetylation, Acetyltransferases, Amino Acid Sequence, Cell Cycle Proteins, Cell Line, Cytoskeletal Proteins, DNA-Binding Proteins, Genes, Reporter, Histone Acetyltransferases, Humans, Lysine, Molecular Sequence Data, Peptides, Protein Binding, Protein Structure, Tertiary, Proto-Oncogene Proteins, Recombinant Fusion Proteins, TCF Transcription Factors, Trans-Activators, Transcription Factor 7-Like 2 Protein, Transcription Factors, Transcription, Genetic, Wnt Proteins, Zebrafish Proteins, beta Catenin, p300-CBP Transcription Factors
Mol. Cell. Biol.
Date: Apr. 01, 2004
PubMed ID: 15060161
View in: Pubmed Google Scholar
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