期刊
ONCOGENE
卷 33, 期 13, 页码 1690-1699出版社
SPRINGERNATURE
DOI: 10.1038/onc.2013.113
关键词
GSK-3; translation; 4E-BP1
资金
- University of Cincinnati College of Medicine
- Marlene Harris-Ride Cincinnati Breast Cancer Pilot Grant Program
- Canadian Cancer Society Research Institute
- Cancer Research Society
- Cancer Prevention and Research Institute of Texas [R1103]
- Welch Foundation [I-1800]
- University of Texas Southwestern Medical Center
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)-3 beta promotes cell proliferation through positive regulation of protein synthesis. We found that GSK-3 beta 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.
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