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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.

Pubmed ID: 18987336


  • Ge X
  • Jin Q
  • Zhang F
  • Yan T
  • Zhai Q


Molecular biology of the cell

Publication Data

January 1, 2009

Associated Grants


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