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PCAF acetylates {beta}-catenin and improves its stability.

http://www.ncbi.nlm.nih.gov/pubmed/18987336

beta-Catenin plays an important role in development and tumorigenesis. However, the effect of a key acetyltransferase p300/CBP-associated factor (PCAF) on beta-catenin signaling is largely unknown. In this study, we found PCAF could increase the beta-catenin transcriptional activity, induce its nuclear translocation, and up-regulate its protein level by inhibiting its ubiquitination and improving its stability. Further studies showed that PCAF directly binds to and acetylates beta-catenin. The key ubiquitination sites Lys-19 and Lys-49 of beta-catenin were shown as the critical residues for PCAF-induced acetylation and stabilization. Knockdown of PCAF in colon cancer cells markedly reduced the protein level, transcriptional activity, and acetylation level of beta-catenin; promoted cell differentiation; inhibited cell migration; and repressed xenografted tumorigenesis and tumor growth in nude mice. All these data demonstrate that PCAF acetylates beta-catenin and regulates its stability, and they raise the prospect that therapies targeting PCAF may be of clinical use in beta-catenin-driven diseases, such as colon cancer.

Pubmed ID: 18987336 RIS Download

Mesh terms: Acetylation | Animals | Cell Differentiation | Cell Line, Tumor | Cell Movement | Colonic Neoplasms | Humans | Lysine | Male | Mice | Mice, Inbred BALB C | Mice, Nude | Neoplasm Transplantation | Protein Stability | Signal Transduction | Transcriptional Activation | Wnt Proteins | beta Catenin | p300-CBP Transcription Factors

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