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Updated: Aug 8, 2026
Eukaryotic Polyribosome Profile Analysis
Published on: June 15, 2010
Ribosomal protein S6 phosphorylation: from protein synthesis to cell size
1Department of Biochemistry, The Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Abstract:
Recent studies are beginning to disclose a signaling network involved in regulating cell size. Although many links and effectors are still unknown, central components of this network include the mammalian target of rapamycin (mTOR) and its downstream effectors - the ribosomal protein S6 kinase (S6K) and the translational repressor eukaryotic initiation factor 4E-binding protein. Until recently, the role of S6K and its many substrates in cell-size control remained obscure; however, a knockin mouse carrying mutations at all phosphorylation sites in the primary S6K substrate, ribosomal protein S6 (rpS6), has provided insight into the physiological role of this protein phosphorylation event. In addition to its role in glucose homeostasis in the whole mouse, phosphorylation of rpS6 is essential for regulating the size of at least some cell types, but is dispensable for translational control of mRNAs with a 5' terminal oligopyrimidine tract (TOP mRNAs) - its previously assigned targets. It therefore seems that establishing the function of the phosphorylation of other effectors of mTOR or S6K will inevitably require genetic manipulation of the respective sites within these targets.
Insights
Cell size regulation involves the mTOR signaling network. Phosphorylation of ribosomal protein S6 (rpS6) is crucial for cell size, but not for TOP mRNA translation, requiring further genetic studies.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Cell size is a fundamental biological parameter regulated by complex signaling networks.
- The mammalian target of rapamycin (mTOR) pathway, including S6 kinase (S6K) and eukaryotic initiation factor 4E-binding protein, plays a central role in cell growth.
- The precise function of S6K substrates, particularly ribosomal protein S6 (rpS6) phosphorylation, in cell-size control remained largely unknown.
Purpose of the Study:
- To elucidate the physiological role of rpS6 phosphorylation in cell-size regulation.
- To investigate the involvement of rpS6 phosphorylation in translational control of specific mRNA types.
Main Methods:
- Generation of a knockin mouse model with mutations at all rpS6 phosphorylation sites.
- Analysis of cell size and glucose homeostasis in the mutant mouse.
- Assessment of TOP mRNA translation efficiency in the context of rpS6 mutations.
Main Results:
- Phosphorylation of rpS6 is essential for regulating the size of certain cell types.
- rpS6 phosphorylation is dispensable for the translational control of 5' terminal oligopyrimidine tract (TOP) mRNAs.
- rpS6 phosphorylation also contributes to glucose homeostasis in the whole mouse.
Conclusions:
- The study identifies rpS6 phosphorylation as a key regulator of cell size, independent of its previously presumed role in TOP mRNA translation.
- Further genetic manipulation of mTOR and S6K effectors is necessary to fully understand their roles in cellular regulation.
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