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 |
Fingerprint
Keywords
- 4E-BP1
- GSK-3
- Translation
ASJC Scopus subject areas
- Molecular Biology
- Cancer Research
- Genetics
Cite this
Glycogen synthase kinase-3β positively regulates protein synthesis and cell proliferation through the regulation of translation initiation factor 4E-binding protein 1. / Shin, S.; Wolgamott, L.; Tcherkezian, J.; Vallabhapurapu, S.; Yu, Y.; Roux, P. P.; Yoon, S. O.
In: Oncogene, Vol. 33, No. 13, 27.03.2014, p. 1690-1699.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glycogen synthase kinase-3β positively regulates protein synthesis and cell proliferation through the regulation of translation initiation factor 4E-binding protein 1
AU - Shin, S.
AU - Wolgamott, L.
AU - Tcherkezian, J.
AU - Vallabhapurapu, S.
AU - Yu, Y.
AU - Roux, P. P.
AU - Yoon, S. O.
PY - 2014/3/27
Y1 - 2014/3/27
N2 - 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.
AB - 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.
KW - 4E-BP1
KW - GSK-3
KW - Translation
UR - http://www.scopus.com/inward/record.url?scp=84898014860&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84898014860&partnerID=8YFLogxK
U2 - 10.1038/onc.2013.113
DO - 10.1038/onc.2013.113
M3 - Article
C2 - 23584478
AN - SCOPUS:84898014860
VL - 33
SP - 1690
EP - 1699
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 13
ER -