ArticleInternational journal of molecular sciences2022
UDP-Glucose: A Cereblon-Dependent Glucokinase Protein Degrader.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 9 citations in OpenAlex.
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Glucose limitation protects cancer cells from apoptosis induced by pyrimidine restriction and replication inhibition.Nature metabolism · 2024Article
- Glucokinase Variant Proteins Are Resistant to Fasting-Induced Uridine Diphosphate Glucose-Dependent Degradation in Maturity-Onset Diabetes of the Young Type 2 Patients.International journal of molecular sciences · 2023Article
- Regulation of Ubiquitin Family Signaling in Disease.International journal of molecular sciences · 2023Article
- UDP-glucose, cereblon-dependent proinsulin degrader.Scientific reports · 2022Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
We previously reported that glucokinase is ubiquitinated and degraded by cereblon with an unknown endogenous glucokinase protein degrader. Here, we show that UDP-glucose is a glucokinase protein degrader. We identified that both glucose and UDP-glucose bind to glucokinase and that both uridine and UDP-glucose bind to cereblon in a similar way to thalidomide. From these results, UDP-glucose was identified as a molecular glue between cereblon and glucokinase. Glucokinase produces glucose-6-phosphate in the pancreas and liver. Especially in β-cells, glucokinase is the main target of glucose for glucose-induced insulin secretion. UDP-glucose administration ubiquitinated and degraded glucokinase, lowered glucose-6-phosphate production, and then reduced insulin secretion in β-cell lines and mice. Maturity-onset diabetes of the young type 2 (MODY2) glucokinase
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Registered trials
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