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.
Original language | English (US) |
---|---|
Pages (from-to) | 1690-1699 |
Number of pages | 10 |
Journal | Oncogene |
Volume | 33 |
Issue number | 13 |
DOIs | |
State | Published - Mar 27 2014 |
Keywords
- 4E-BP1
- GSK-3
- Translation
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Cancer Research