ArticleInvestigative ophthalmology & visual science2016
The Translational Repressor 4E-BP1 Contributes to Diabetes-Induced Visual Dysfunction.
Article in Investigative ophthalmology & visual science, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Role of O-GlcNAcylation in Central Nervous System Development and Injuries: A Systematic Review.Molecular neurobiology · 2024Pooled it
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- Recent Advances in Understanding the Role of PEST Sequence- Containing Proteins in Retinal Neovascularization.Current drug targets · 2025Review
- NLRP3 Inflammasome Priming in the Retina of Diabetic Mice Requires REDD1-Dependent Activation of GSK3β.Investigative ophthalmology & visual science · 2024Article
- Activation of Disulfide Redox Switch in REDD1 Promotes Oxidative Stress Under Hyperglycemic Conditions.Diabetes · 2022Article
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- Müller Glial Expression of REDD1 Is Required for Retinal Neurodegeneration and Visual Dysfunction in Diabetic Mice.Diabetes · 2022Article
- Post-transcriptional control by RNA-binding proteins in diabetes and its related complications.Frontiers in physiology · 2022Review
- Retinal Protein O-GlcNAcylation and the Ocular Renin-angiotensin System: Signaling Cross-roads in Diabetic Retinopathy.Current diabetes reviews · 2022Article
- Feedback Regulation ofInternational journal of molecular sciences · 2021Article
- Diabetes enhances translation ofThe Journal of biological chemistry · 2020Article
- REDD1 Activates a ROS-Generating Feedback Loop in the Retina of Diabetic Mice.Investigative ophthalmology & visual science · 2019Article
- Article
- Emerging roles of RNA-binding proteins in diabetes and their therapeutic potential in diabetic complications.Wiley interdisciplinary reviews. RNA · 2018Review
- Cross-Dysregulation ofFrontiers in endocrinology · 2018Review
- Deletion of the Akt/mTORC1 Repressor REDD1 Prevents Visual Dysfunction in a Rodent Model of Type 1 Diabetes.Diabetes · 2018Article
- Diabetic retinopathy: current understanding, mechanisms, and treatment strategies.JCI insight · 2017Review
- Activation of the Stress Response Kinase JNK (c-Jun N-terminal Kinase) Attenuates Insulin Action in Retina through a p70S6K1-dependent Mechanism.The Journal of biological chemistry · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
purposeThe translational repressor 4E-BP1 interacts with the mRNA cap-binding protein eIF4E and thereby promotes cap-independent translation of mRNAs encoding proteins that contribute to diabetic retinopathy. Interaction of 4E-BP1 with eIF4E is enhanced in the retina of diabetic rodents, at least in part, as a result of elevated 4E-BP1 protein expression. In the present study, we examined the role of 4E-BP1 in diabetes-induced visual dysfunction, as well as the mechanism whereby hyperglycemia promotes 4E-BP1 expression.
methodsNondiabetic and diabetic wild-type and 4E-BP1/2 knockout mice were evaluated for visual function using a virtual optomotor test (Optomotry). Retinas were harvested from nondiabetic and type 1 diabetic mice and analyzed for protein abundance and posttranslational modifications. Similar analyses were performed on cells in culture exposed to hyperglycemic conditions or an O-GlcNAcase inhibitor (Thiamet G [TMG]).
resultsDiabetes-induced visual dysfunction was delayed in mice deficient of 4E-BP1/2 as compared to controls. 4E-BP1 protein expression was enhanced by hyperglycemia in the retina of diabetic rodents and by hyperglycemic conditions in retinal cells in culture. A similar elevation in 4E-BP1 expression was observed with TMG. The rate of 4E-BP1 degradation was significantly prolonged by either hyperglycemic conditions or TMG. A PEST motif in the C-terminus of 4E-BP1 regulated polyubiquitination, turnover, and binding of an E3 ubiquitin ligase complex containing CUL3.
conclusionsThe findings support a model whereby elevated 4E-BP1 expression observed in the retina of diabetic rodents is the result of O-GlcNAcylation of 4E-BP1 within its PEST motif.
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