PCAF Acetylates β-catenin and improves its stability

Xinjian Ge, Qihuang Jin, Fang Zhang, Tingting Yan, Qiwei Zhai

Research output: Contribution to journalArticle

80 Scopus citations

Abstract

β-Catenin plays an important role in development and tumorigenesis. However, the effect of a key acetyltransferase p300/CBP-associated factor (PCAF) on β-catenin signaling is largely unknown. In this study, we found PCAF could increase the β-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 β-catenin. The key ubiquitination sites Lys-19 and Lys-49 of β-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 β-catenin; promoted cell differentiation; inhibited cell migration; and repressed xenografted tumorigenesis and tumor growth in nude mice. All these data demonstrate that PCAF acetylates β-catenin and regulates its stability, and they raise the prospect that therapies targeting PCAF may be of clinical use in β-catenin-driven diseases, such as colon cancer.

Original languageEnglish (US)
Pages (from-to)419-427
Number of pages9
JournalMolecular biology of the cell
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2009

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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