Investigation of the molecular mechanism of δ-catenin ubiquitination: Implication of β-TrCP-1 as a potential E3 ligase.

Ubiquitination, a post-translational modification, involves the covalent attachment of ubiquitin to the target protein. The ubiquitin-proteasome pathway and the endosome-lysosome pathway control the degradation of the majority of eukaryotic proteins. Our previous study illustrated that δ-catenin ubiquitination occurs in a glycogen synthase kinase-3 (GSK-3) phosphorylation-dependent manner. However, the molecular mechanism of δ-catenin ubiquitination is still unknown. Here, we show that the lysine residues required for ubiquitination are located mainly in the C-terminal portion of δ-catenin. In addition, we provide evidence that β-TrCP-1 interacts with δ-catenin and functions as an E3 ligase, mediating δ-catenin ubiquitin-proteasome degradation. Furthermore, we prove that both the ubiquitin-proteasome pathway and the lysosome degradation pathway are involved in δ-catenin degradation. Our novel findings on the mechanism of δ-catenin ubiquitination will add a new perspective to δ-catenin degradation and the effects of δ-catenin on E-cadherin involved in epithelial cell-cell adhesion, which is implicated in prostate cancer progression.

Biochimica et biophysica acta. 2016 Jun 15 [Epub ahead of print]

Hridaya Shrestha, Tingting Yuan, Yongfeng He, Pyong-Gon Moon, Nensi Shrestha, Taeyong Ryu, So-Yeon Park, Young-Chang Cho, Chan-Hyeong Lee, Moon-Chang Baek, Sayeon Cho, Shishli Simkhada, Hangun Kim, Kwonsep Kim

College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea., College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea., College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea., Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea., College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea., College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea., College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, 540-950, Republic of Korea., College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea., Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea., Department of Molecular Medicine, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422, Republic of Korea., College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea., College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea., College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, 540-950, Republic of Korea., College of Pharmacy and Research Institute for Drug Development, Chonnam National University, Gwangju 500-757, Republic of Korea.