Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5509399 | Cellular Signalling | 2017 | 11 Pages |
â¢Hakai increases the stability of δ-catenin regardless of its E3 ligase activity.â¢Hakai and δ-catenin do not associate physically.â¢Hakai stabilizes δ-catenin through Src kinase.â¢Î´-Catenin mainly localizes in the plasma membrane regardless of E-cadherin endocytosis after Hakai overexpression.
Hakai ubiquitinates and induces endocytosis of the E-cadherin complex; thus, modulating cell adhesion and regulating development of the epithelial-mesenchymal transition of metastasis. Our previous published data show that δ-catenin promotes E-cadherin processing and thereby activates β-catenin-mediated oncogenic signals. Although several published data show the interactions between δ-catenin and E-cadherin and between Hakai and E-cadherin separately, we found no published report on the relationship between δ-catenin and Hakai. In this report, we show Hakai stabilizes δ-catenin regardless of its E3 ligase activity. We show that Hakai and Src increase the stability of δ-catenin synergistically. Hakai stabilizes Src and Src, which in turn, inhibits binding between glycogen synthase kinase-3β and δ-catenin, resulting in less proteosomal degradation of δ-catenin. These results suggest that stabilization of δ-catenin by Hakai is dependent on Src.