TY - JOUR
T1 - PCAF Acetylates β-catenin and improves its stability
AU - Ge, Xinjian
AU - Jin, Qihuang
AU - Zhang, Fang
AU - Yan, Tingting
AU - Zhai, Qiwei
PY - 2009/1/1
Y1 - 2009/1/1
N2 - 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.
AB - 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.
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U2 - 10.1091/mbc.E08-08-0792
DO - 10.1091/mbc.E08-08-0792
M3 - Article
C2 - 18987336
AN - SCOPUS:63049111216
SN - 1059-1524
VL - 20
SP - 419
EP - 427
JO - Molecular biology of the cell
JF - Molecular biology of the cell
IS - 1
ER -