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Updated: May 12, 2026

Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
Glycogen synthase kinase-3β positively regulates protein synthesis and cell proliferation through the regulation of
S Shin1, L Wolgamott1, J Tcherkezian2
1Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Abstract:
Protein synthesis has a key role in the control of cell proliferation, and its deregulation is associated with pathological conditions, notably cancer. Rapamycin, an inhibitor of mammalian target of rapamycin complex 1 (mTORC1), was known to inhibit protein synthesis. However, it does not substantially inhibit protein synthesis and cell proliferation in many cancer types. We were interested in finding a novel target in rapamycin-resistant cancer. The rate-limiting factor for translation is eukaryotic translation initiation factor 4E (eIF4E), which is negatively regulated by eIF4E-binding protein 1 (4E-BP1). Here, we provide evidence that glycogen synthase kinase (GSK)-3β promotes cell proliferation through positive regulation of protein synthesis. We found that GSK-3β phosphorylates and inactivates 4E-BP1, thereby increasing eIF4E-dependent protein synthesis. Considering the clinical relevance of pathways regulating protein synthesis, our study provides a promising new strategy and target for cancer therapy.
Insights
Glycogen synthase kinase-3 beta (GSK-3β) promotes cancer cell proliferation by increasing protein synthesis. Inhibiting GSK-3β may offer a new strategy against rapamycin-resistant cancers.
Area of Science:
- Molecular Biology
- Cancer Research
- Biochemistry
Background:
- Protein synthesis is crucial for cell proliferation and is often deregulated in cancer.
- Rapamycin, an mTORC1 inhibitor, has limited efficacy in many cancer types due to resistance.
- Identifying novel targets in rapamycin-resistant cancer is essential for developing new therapies.
Purpose of the Study:
- To identify novel therapeutic targets in rapamycin-resistant cancers.
- To investigate the role of glycogen synthase kinase-3 beta (GSK-3β) in regulating protein synthesis and cell proliferation.
- To explore GSK-3β as a potential target for cancer therapy.
Main Methods:
- Investigated the role of GSK-3β in regulating protein synthesis and cell proliferation.
- Examined the phosphorylation and inactivation of eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) by GSK-3β.
- Assessed the impact of GSK-3β activity on eukaryotic translation initiation factor 4E (eIF4E)-dependent protein synthesis.
Main Results:
- GSK-3β was found to promote cell proliferation by positively regulating protein synthesis.
- GSK-3β phosphorylates and inactivates 4E-BP1.
- This inactivation of 4E-BP1 leads to increased eIF4E-dependent protein synthesis.
Conclusions:
- GSK-3β plays a significant role in promoting cancer cell proliferation via enhanced protein synthesis.
- Targeting GSK-3β represents a promising new therapeutic strategy for rapamycin-resistant cancers.
- Understanding the GSK-3β/4E-BP1/eIF4E pathway offers insights into cancer progression and treatment.
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