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Updated: Jan 28, 2026

Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
Published on: September 17, 2012
Cyclin D1 Stability Is Partly Controlled by O-GlcNAcylation
Louis Masclef1, Vanessa Dehennaut2, Marlène Mortuaire1
1Université de Lille, CNRS, UMR 8576, UGSF, Unité de Glycobiologie Structurale et Fonctionnelle, Lille, France.
O-GlcNAcylation stabilizes cyclin D1, a key cell cycle regulator. This process, mediated by O-GlcNAc transferase (OGT), involves O-GlcNAcylation of cyclin D1, reducing its ubiquitination and degradation.
Area of Science:
- Molecular Biology
- Cellular Biology
- Biochemistry
Background:
- Cyclin D1 partners with CDK4/CDK6 to regulate cell cycle entry and G1 progression.
- Cyclin D1 stability is crucial and tightly controlled by phosphorylation and ubiquitination.
- The role of O-linked β-N-Acetyl-glucosaminylation (O-GlcNAcylation) in cyclin D1 regulation was previously unexplored.
Purpose of the Study:
- To investigate the impact of O-GlcNAcylation on cyclin D1 stability and turnover.
- To elucidate the mechanism by which O-GlcNAcylation affects cyclin D1 ubiquitination.
- To determine if O-GlcNAc transferase (OGT) directly interacts with and modifies cyclin D1.
Main Methods:
- Biochemical assays to assess cyclin D1 stability under varying O-GlcNAc levels.
- O-GlcNAcase (OGA) inhibition to elevate cellular O-GlcNAc.
- Ubiquitination assays to quantify cyclin D1 modification.
- Cell imaging and co-immunoprecipitation to detect OGT-cyclin D1 interaction.
Main Results:
- Elevated O-GlcNAc levels significantly increase cyclin D1 half-life.
- Reduced O-GlcNAcylation leads to a marked decrease in cyclin D1 stability.
- OGA inhibition slows down cyclin D1 ubiquitination.
- OGT directly binds to and glycosylates cyclin D1 in human cancer cells.
Conclusions:
- O-GlcNAcylation is a novel regulatory mechanism controlling cyclin D1 stability.
- O-GlcNAcylation promotes cyclin D1 stability by inhibiting its ubiquitination.
- This finding reveals a new layer of post-translational modification impacting cell cycle control.
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