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http://purl.uniprot.org/citations/32475820http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/32475820http://www.w3.org/2000/01/rdf-schema#comment"Activation of the immune costimulatory molecule cluster of differentiation 40 (CD40) in Müller glia has been implicated in the initiation of diabetes-induced retinal inflammation. Results from previous studies support that CD40 protein expression is elevated in Müller glia of diabetic mice; however, the mechanisms responsible for this increase have not been explored. Here, we evaluated the hypothesis that diabetes augments translation of the Cd40 mRNA. Mice receiving thiamet G (TMG), an inhibitor of the O-GlcNAc hydrolase O-GlcNAcase, exhibited enhanced retinal protein O-GlcNAcylation and increased Cd40 mRNA translation. TMG administration also promoted Cd40 mRNA association with Müller cell-specific ribosomes isolated from the retina of RiboTag mice. Similar effects on O-GlcNAcylation and Cd40 mRNA translation were also observed in the retina of a mouse model of type 1 diabetes. In cultured cells, TMG promoted sequestration of the cap-binding protein eIF4E (eukaryotic translation in initiation factor 4E) by 4E-BP1 (eIF4E-binding protein 1) and enhanced cap-independent Cd40 mRNA translation as assessed by a bicistronic reporter that contained the 5'-UTR of the Cd40 mRNA. Ablation of 4E-BP1/2 prevented the increase in Cd40 mRNA translation in TMG-exposed cells, and expression of a 4E-BP1 variant that constitutively sequesters eIF4E promoted reporter activity. Extending on the cell culture results, we found that in contrast to WT mice, diabetic 4E-BP1/2-deficient mice did not exhibit enhanced retinal Cd40 mRNA translation and failed to up-regulate expression of the inflammatory marker nitric-oxide synthase 2. These findings support a model wherein diabetes-induced O-GlcNAcylation of 4E-BP1 promotes Cd40 mRNA translation in Müller glia."xsd:string
http://purl.uniprot.org/citations/32475820http://purl.org/dc/terms/identifier"doi:10.1074/jbc.ra120.013711"xsd:string
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/author"Dennis M.D."xsd:string
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/author"Sunilkumar S."xsd:string
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/author"Miller W.P."xsd:string
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/author"Dierschke S.K."xsd:string
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/author"Toro A.L."xsd:string
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/date"2020"xsd:gYear
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/pages"10831-10841"xsd:string
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/title"Diabetes enhances translation of Cd40 mRNA in murine retinal Muller glia via a 4E-BP1/2-dependent mechanism."xsd:string
http://purl.uniprot.org/citations/32475820http://purl.uniprot.org/core/volume"295"xsd:string
http://purl.uniprot.org/citations/32475820http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/32475820
http://purl.uniprot.org/citations/32475820http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/32475820
http://purl.uniprot.org/uniprot/#_P70445-mappedCitation-32475820http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32475820
http://purl.uniprot.org/uniprot/#_A2A5L7-mappedCitation-32475820http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32475820
http://purl.uniprot.org/uniprot/#_P27512-mappedCitation-32475820http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32475820
http://purl.uniprot.org/uniprot/#_Q3UZD4-mappedCitation-32475820http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32475820
http://purl.uniprot.org/uniprot/#_Q3UFP6-mappedCitation-32475820http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32475820
http://purl.uniprot.org/uniprot/#_Q3TII9-mappedCitation-32475820http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32475820
http://purl.uniprot.org/uniprot/#_Q60876-mappedCitation-32475820http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32475820
http://purl.uniprot.org/uniprot/#_S4R2M8-mappedCitation-32475820http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/32475820
http://purl.uniprot.org/uniprot/P70445http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/32475820
http://purl.uniprot.org/uniprot/Q3UFP6http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/32475820