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Sci Rep. 2019 Mar 4;9(1):3351. doi: 10.1038/s41598-019-40238-w.

p300/CBP-associated factor promotes autophagic degradation of δ-catenin through acetylation and decreases prostate cancer tumorigenicity.

Author information

1
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea.
2
Korea Basic Science Institute, Gwangju Center, Gwangju, Republic of Korea.
3
Department of Environmental Engineering, Sunchon National University, Sunchon, Republic of Korea.
4
Department of Pharmacology, Chonnam National University Medical School, Gwangju, Republic of Korea.
5
College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju, Republic of Korea.
6
College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, Republic of Korea. hangunkim@sunchon.ac.kr.

Abstract

δ-Catenin shares common binding partners with β-catenin. As acetylation and deacetylation regulate β-catenin stability, we searched for histone acetyltransferases (HATs) or histone deacetylases (HDACs) affecting δ-catenin acetylation status and protein levels. We showed that p300/CBP-associated factor (PCAF) directly bound to and acetylated δ-catenin, whereas several class I and class II HDACs reversed this effect. Unlike β-catenin, δ-catenin was downregulated by PCAF-mediated acetylation and upregulated by HDAC-mediated deacetylation. The HDAC inhibitor trichostatin A attenuated HDAC1-mediated δ-catenin upregulation, whereas HAT or autophagy inhibitors, but not proteasome inhibitors, abolished PCAF-mediated δ-catenin downregulation. The results suggested that PCAF-mediated δ-catenin acetylation promotes its autophagic degradation in an Atg5/LC3-dependent manner. Deletions or point mutations identified several lysine residues in different δ-catenin domains involved in PCAF-mediated δ-catenin downregulation. PCAF overexpression in prostate cancer cells markedly reduced δ-catenin levels and suppressed cell growth and motility. PCAF-mediated δ-catenin downregulation inhibited E-cadherin processing and decreased the nuclear distribution of β-catenin, resulting in the suppression of β-catenin/LEF-1-mediated downstream effectors. These data demonstrate that PCAF downregulates δ-catenin by promoting its autophagic degradation and suppresses δ-catenin-mediated oncogenic signals.

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