| http://purl.uniprot.org/citations/24616100 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/24616100 | http://www.w3.org/2000/01/rdf-schema#comment | "Wnt signaling plays a pivotal role in cell proliferation, tissue homeostasis, and tumorigenesis. Dishevelled (Dvl) is a central node of Wnt signaling. Insulin receptor substrates (IRSs), as a critical component of insulin signaling, are involved in cell proliferation, metabolism, and cancer development. In this study, we report that IRS1/2 promotes Wnt/β-catenin signaling by stabilizing Dvl2. We found that IRS1/2 interacts with Dvl2. Overexpression of IRS1/2 increased the protein level of Dvl2 and promoted canonical Wnt signaling, as evidenced by the increased T cell-specific factor 4 transcriptional activity and the up-regulation of expression of CYCLIN D1 and c-MYC, two Wnt target genes critical for cell growth, whereas depletion of IRS1/2 reduced the level of Dvl2 and attenuated Wnt/β-catenin signaling. Biochemical analyses revealed that IRS1/2 decreased Lys-63-linked ubiquitination of Dvl2 and stabilized Dvl2 protein via suppressing its autophagy-mediated degradation. We further revealed that IRS1/2 blocks autophagy-induced formation of the Dvl2-p62/SQSTM1 complex, resulting in disabled association of Dvl2 to autophagosomes. We demonstrated that IRS1/2 promoted the induction of epithelial-mesenchymal transition (EMT) and cell proliferation in response to Wnt stimulation, whereas depletion of Dvl2 impaired the IRS1/2-mediated EMT and cell growth. Our findings revealed that IRS1/2 promotes EMT and cell proliferation through stabilizing Dvl2."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m113.544999"xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Geng Y."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Jin L."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Li Y."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Jia B."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Qiu Y."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Wang Y."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Ren F."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Wei C."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Kishida M."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Ju Y."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Chang Z."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Tomita Y."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Su F."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/author | "Tomoeda M."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/date | "2014"xsd:gYear |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/pages | "11230-11241"xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/title | "Insulin receptor substrate 1/2 (IRS1/2) regulates Wnt/beta-catenin signaling through blocking autophagic degradation of dishevelled2."xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://purl.uniprot.org/core/volume | "289"xsd:string |
| http://purl.uniprot.org/citations/24616100 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/24616100 |
| http://purl.uniprot.org/citations/24616100 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/24616100 |
| http://purl.uniprot.org/uniprot/#_B4DM44-mappedCitation-24616100 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/24616100 |