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Glucocorticoids abate p70(S6k) and eIF4E function in L6 skeletal myoblasts
O J Shah1, S R Kimball, L S Jefferson
1Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA.
Summary
Glucocorticoids, like dexamethasone, inhibit protein synthesis by deactivating key signaling pathways. This research shows how these hormones impact translation initiation factors in muscle cells.
Area of Science:
- Molecular Biology
- Endocrinology
- Cellular Signaling
Background:
- Glucocorticoid hormones regulate protein degradation and synthesis.
- Glucocorticoids influence the translational machinery, specifically translation initiation.
- Understanding glucocorticoid effects on protein synthesis is crucial for metabolic research.
Purpose of the Study:
- To investigate the mechanism by which glucocorticoids, specifically dexamethasone, affect protein synthesis initiation in L6 myoblasts.
- To identify the specific molecular targets and signaling pathways involved in glucocorticoid-mediated inhibition of translation.
Main Methods:
- Treatment of L6 myoblasts with dexamethasone.
- Analysis of phosphorylation status of ribosomal protein S6 kinase (p70(S6k)) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1).
- Assessment of protein phosphatase activity using okadaic acid and calyculin A.
Main Results:
- Dexamethasone deactivated p70(S6k) by reducing its phosphorylation at Thr(389).
- Glucocorticoid administration induced dephosphorylation of 4E-BP1, facilitating its binding to eIF4E.
- Protein phosphatase 1 (PP1) and/or 2A (PP2A) activity appears to mediate these dephosphorylation events.
Conclusions:
- Glucocorticoids attenuate distal components of the phosphatidylinositol-3 kinase signaling pathway.
- This attenuation leads to the encumbrance of the cellular protein synthetic apparatus.
- The findings elucidate a novel mechanism for glucocorticoid control over protein synthesis.