| http://purl.uniprot.org/citations/31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31300553 | http://www.w3.org/2000/01/rdf-schema#comment | "An early hallmark of type 2 diabetes is a failure of proinsulin-to-insulin processing in pancreatic β-cells, resulting in hyperproinsulinemia. Proinsulin processing is quite sensitive to nutrient flux, and β-cell-specific deletion of the nutrient-sensing protein modifier OGlcNAc transferase (βOGTKO) causes β-cell failure and diabetes, including early development of hyperproinsulinemia. The mechanisms underlying this latter defect are unknown. Here, using several approaches, including site-directed mutagenesis, Click O-GlcNAc labeling, immunoblotting, and immunofluorescence and EM imaging, we provide the first evidence for a relationship between the O-GlcNAcylation of eukaryotic translation initiation factor 4γ1 (eIF4G1) and carboxypeptidase E (CPE)-dependent proinsulin processing in βOGTKO mice. We first established that βOGTKO hyperproinsulinemia is independent of age, sex, glucose levels, and endoplasmic reticulum-CCAAT enhancer-binding protein homologous protein (CHOP)-mediated stress status. Of note, OGT loss was associated with a reduction in β-cell-resident CPE, and genetic reconstitution of CPE in βOGTKO islets rescued the dysfunctional proinsulin-to-insulin ratio. We show that although CPE is not directly OGlcNAc modified in islets, overexpression of the suspected OGT target eIF4G1, previously shown to regulate CPE translation in β-cells, increases islet CPE levels, and fully reverses βOGTKO islet-induced hyperproinsulinemia. Furthermore, our results reveal that OGT O-GlcNAc-modifies eIF4G1 at Ser-61 and that this modification is critical for eIF4G1 protein stability. Together, these results indicate a direct link between nutrient-sensitive OGT and insulin processing, underscoring the importance of post-translational O-GlcNAc modification in general cell physiology."xsd:string |
| http://purl.uniprot.org/citations/31300553 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra119.008670"xsd:string |
| http://purl.uniprot.org/citations/31300553 | http://purl.uniprot.org/core/author | "Jo S."xsd:string |
| http://purl.uniprot.org/citations/31300553 | http://purl.uniprot.org/core/author | "Lockridge A."xsd:string |
| http://purl.uniprot.org/citations/31300553 | http://purl.uniprot.org/core/author | "Alejandro E.U."xsd:string |
| http://purl.uniprot.org/citations/31300553 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31300553 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/31300553 | http://purl.uniprot.org/core/pages | "13040-13050"xsd:string |
| http://purl.uniprot.org/citations/31300553 | http://purl.uniprot.org/core/title | "eIF4G1 and carboxypeptidase E axis dysregulation in pii>O-pi/i>GlcNAc transferase-deficient pancreatic beta-cells contributes to hyperproinsulinemia in mice."xsd:string |
| http://purl.uniprot.org/citations/31300553 | http://purl.uniprot.org/core/volume | "294"xsd:string |
| http://purl.uniprot.org/citations/31300553 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31300553 |
| http://purl.uniprot.org/citations/31300553 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/31300553 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YTV0-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YU44-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YUC1-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_E9Q9E1-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YUL1-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YUS5-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_A0A0J9YVC1-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_D3YWC6-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_D3YWM1-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_D3YWY7-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_D3YX14-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |
| http://purl.uniprot.org/uniprot/#_E9Q770-mappedCitation-31300553 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/31300553 |