title: Hakai, an E3-ligase for E-cadherin, stabilizes δ-catenin through Src kinase.
abstract: 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.
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Hridaya
authors.initials: H
authors.lastname: Shrestha
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Taeyong
authors.initials: T
authors.lastname: Ryu
authors.affiliation: Korea Basic Science Institute, Gwangju Center at Chonnam National University, Gwangju, South Korea.
authors.forename: Young-Woo
authors.initials: YW
authors.lastname: Seo
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, South Korea.
authors.forename: So-Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: He
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Weiye
authors.initials: W
authors.lastname: Dai
authors.affiliation: Korea Basic Science Institute, Gwangju Center at Chonnam National University, Gwangju, South Korea.
authors.forename: Eunsook
authors.initials: E
authors.lastname: Park
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea.
authors.forename: Shishli
authors.initials: S
authors.lastname: Simkhada
authors.affiliation: College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon, South Korea.
authors.forename: Hangun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, Gwangju, South Korea. Electronic address: klee@jnu.ac.kr.
authors.forename: Keesook
authors.initials: K
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Research Institute for Drug Development, Chonnam National University, Gwangju, South Korea. Electronic address: koskim@jnu.ac.kr.
authors.forename: Kwonseop
authors.initials: K
authors.lastname: Kim
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D017353:Gene Deletion; D006801:Humans; D008954:Models, Biological; D011485:Protein Binding; D055550:Protein Stability; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D019061:src-Family Kinases / Q000378:metabolism*; D000095002:Delta Catenin
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D051177:Catenins; D011993:Recombinant Fusion Proteins; C471638:CBLL1 protein, human; D044767:Ubiquitin-Protein Ligases; D019061:src-Family Kinases; D000095002:Delta Catenin
keywords: E-cadherin; Hakai; δ-Catenin