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MBC in Press, published online ahead of print November 5, 2008
Mol. Biol. Cell 10.1091/mbc.E08-08-0792

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Submitted on August 1, 2008
Revised on October 22, 2008
Accepted on October 29, 2008

PCAF Acetylates {beta}-Catenin and Improves Its Stability

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

Key Laboratory of Nutrition and Metabolism, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences; Graduate School of the Chinese Academy of Sciences, Shanghai 200031, China

Monitoring Editor: Mark H. Ginsberg

{beta}-Catenin plays an important role in development and tumorigenesis. However the effect of a key acetyltransferase 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 raise the prospect that therapies targeting PCAF may be of clinical use in {beta}-catenin-driven diseases, such as colon cancer.

Address correspondence to: Qiwei Zhai (qwzhai{at}sibs.ac.cn)






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