| http://purl.uniprot.org/citations/26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26147758 | http://www.w3.org/2000/01/rdf-schema#comment | "The transcription factor Gli-similar 3 (Glis3) plays a critical role in the generation of pancreatic ß cells and the regulation insulin gene transcription and has been implicated in the development of several pathologies, including type 1 and 2 diabetes and polycystic kidney disease. However, little is known about the proteins and posttranslational modifications that regulate or mediate Glis3 transcriptional activity. In this study, we identify by mass-spectrometry and yeast 2-hybrid analyses several proteins that interact with the N-terminal region of Glis3. These include the WW-domain-containing HECT E3 ubiquitin ligases, Itch, Smurf2, and Nedd4. The interaction between Glis3 and the HECT E3 ubiquitin ligases was verified by co-immunoprecipitation assays and mutation analysis. All three proteins interact through their WW-domains with a PPxY motif located in the Glis3 N-terminus. However, only Itch significantly contributed to Glis3 polyubiquitination and reduced Glis3 stability by enhancing its proteasomal degradation. Itch-mediated degradation of Glis3 required the PPxY motif-dependent interaction between Glis3 and the WW-domains of Itch as well as the presence of the Glis3 zinc finger domains. Transcription analyses demonstrated that Itch dramatically inhibited Glis3-mediated transactivation and endogenous Ins2 expression by increasing Glis3 protein turnover. Taken together, our study identifies Itch as a critical negative regulator of Glis3-mediated transcriptional activity. This regulation provides a novel mechanism to modulate Glis3-driven gene expression and suggests that it may play a role in a number of physiological processes controlled by Glis3, such as insulin transcription, as well as in Glis3-associated diseases."xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0131303"xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://purl.uniprot.org/core/author | "Williams J.G."xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://purl.uniprot.org/core/author | "Jetten A.M."xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://purl.uniprot.org/core/author | "ZeRuth G.T."xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://purl.uniprot.org/core/author | "Cole Y.C."xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26147758 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://purl.uniprot.org/core/pages | "e0131303"xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://purl.uniprot.org/core/title | "HECT E3 Ubiquitin Ligase Itch Functions as a Novel Negative Regulator of Gli-Similar 3 (Glis3) Transcriptional Activity."xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/26147758 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/26147758 |
| http://purl.uniprot.org/citations/26147758 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/26147758 |
| http://purl.uniprot.org/uniprot/#_A0A0G2JEN5-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z649-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z689-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z6Q5-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_A0A1D5RLH0-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_A0A1D5RM92-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_P61372-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_P63037-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_A2AQH3-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_A0A571BDN7-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |
| http://purl.uniprot.org/uniprot/#_A2A5Z6-mappedCitation-26147758 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/26147758 |