Investigation of the molecular mechanism of delta-catenin ubiquitination: Implication of beta-TrCP-1 as a potential E3 ligase

摘要

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 delta-catenin ubiquitination occurs in a glycogen synthase kinase-3 (GSK-3) phosphorylation-dependent manner. However, the molecular mechanism of delta-catenin ubiquitination is still unknown. Here, we show that the lysine residues required for ubiquitination are located mainly in the C-terminal portion of delta-catenin. In addition, we provide evidence that beta-TrCP-1 interacts with delta-catenin and functions as an E3 ligase, mediating delta-catenin ubiquitin-proteasome degradation. Furthermore, we prove that both the ubiquitin-proteasome pathway and the lysosome degradation pathway are involved in delta-catenin degradation. Our novel findings on the mechanism of delta-catenin ubiquitination will add a new perspective to delta-catenin degradation and the effects of delta-catenin on E-cadherin involved in epithelial cell-cell adhesion, which is implicated in prostate cancer progression. (C) 2016 Published by Elsevier B.V.