PCAF acetylates {beta}-catenin and improves its stability.
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.
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
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
Mol. Biol. Cell
Date: Jan. 01, 2009
PubMed ID: 18987336
View in: Pubmed Google Scholar
Download Curated Data For This Publication
85773
Switch View:
- Interactions 5