title: Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability.
abstract: Presenilin1 (PS1), a protein involved in cellular development, forms functional complexes with beta-catenin, a regulator of Wnt signaling and cell-cell adhesion. In addition, both proteins have been shown to play important roles in disease including cancer and Alzheimer disease. Although PS1 and beta-catenin are found in the same complexes, it is not clear whether they bind directly to each other or a third complex component, like cadherin, may mediate their interactions. Here we show that PS1 and beta-catenin form no detectable complexes in cells that express no cadherin. In contrast, these complexes are readily found in E-cadherin containing cells. Furthermore, binding of both PS1 and beta-catenin to E-cadherin is necessary for the formation of PS1/beta-catenin complexes. Importantly, our data show that binding of PS1 to cadherin mediates the effects of PS1 on the phosphorylation, ubiquitination, and destabilization of beta-catenin. Thus, cadherins mediate both the association of PS1 and beta-catenin and the effects of PS1 on the cellular levels of beta-catenin.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York University, New York, New York 10029, USA.
authors.forename: Geo
authors.initials: G
authors.lastname: Serban
authors.forename: Zen
authors.initials: Z
authors.lastname: Kouchi
authors.forename: Lia
authors.initials: L
authors.lastname: Baki
authors.forename: Anastasios
authors.initials: A
authors.lastname: Georgakopoulos
authors.forename: Claudia M
authors.initials: CM
authors.lastname: Litterst
authors.forename: Junichi
authors.initials: J
authors.lastname: Shioi
authors.forename: Nikolaos K
authors.initials: NK
authors.lastname: Robakis
mesh_terms: D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D003902:Detergents / Q000494:pharmacology; D006801:Humans; D047468:Immunoprecipitation; D046911:Macromolecular Substances / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D053764:Presenilin-1; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism; D051176:beta Catenin / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D015820:Cadherins; D003902:Detergents; D046911:Macromolecular Substances; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D053764:Presenilin-1; D025801:Ubiquitin; D051176:beta Catenin