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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation
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Acetyltransferases / metabolism*
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Amino Acid Sequence
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Cell Cycle Proteins / metabolism*
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Cell Line
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Cytoskeletal Proteins / chemistry
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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DNA-Binding Proteins / metabolism*
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Genes, Reporter
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Histone Acetyltransferases
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Humans
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Lysine / metabolism
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Molecular Sequence Data
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Peptides / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Proto-Oncogene Proteins / metabolism
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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TCF Transcription Factors
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Trans-Activators / chemistry
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factor 7-Like 2 Protein
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Transcription Factors / metabolism*
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Transcription, Genetic
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Wnt Proteins
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Zebrafish Proteins*
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beta Catenin
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p300-CBP Transcription Factors
Substances
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CTNNB1 protein, human
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Cell Cycle Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Peptides
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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TCF Transcription Factors
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TCF7L2 protein, human
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Trans-Activators
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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Wnt Proteins
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Zebrafish Proteins
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beta Catenin
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Acetyltransferases
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Histone Acetyltransferases
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p300-CBP Transcription Factors
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p300-CBP-associated factor
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Lysine