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Coordinate regulation of ribosome biogenesis and function by the ribosomal protein S6 kinase, a key mediator of mTOR function
Abstract
Current understanding of the mechanisms by which cell growth is regulated lags significantly behind our knowledge of the complex processes controlling cell cycle progression. Recent studies suggest that the mammalian target of rapamycin (mTOR) pathway is a key regulator of cell growth via the regulation of protein synthesis. The key mTOR effectors of cell growth are eukaryotic initiation factor 4E-binding protein 1 (4EBP-1) and the ribosomal protein S6 kinase (S6K). Here we will review the current models for mTOR dependent regulation of ribosome function and biogenesis as well as its role in coordinating growth factor and nutrient signaling to facilitate homeostasis of cell growth and proliferation. We will place particular emphasis on the role of S6K1 signaling and will highlight the points of cross talk with other key growth control pathways. Finally, we will discuss the impact of S6K signaling and the consequent feedback regulation of the PI3K/Akt pathway on disease processes including cancer.
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“Activation of p70S6K is mediated by sequential phosphorylation on multiple sites by mTOR and PDK1, which is counteracted by PP2A/B56γ (Hahn et al., 2010; Jastrzebski et al., 2007).”
From PP2A holoenzymes, substrate specificity driving cellular functions and deregulation in cancer (2019) · cites this paper as Jastrzebski et al., 2007
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Metadata
- Authors
- Jastrzebski, K., Hannan, K. M., Tchoubrieva, E. B., Hannan, R. D., & Pearson, R. B.
- Affiliations
- The University of Melbourne (AU)
- Peter MacCallum Cancer Centre (AU)
- Corresponding author
- Pearson, Richard B.
- Venue
- Growth Factors
- Publisher
- Informa UK Limited
- Published
- 2007-01
- Volume
- 25
- Issue
- 4
- Pages
- 209-226
- ISSN
- 0897-7194 (ISSN-L)
- 1029-2292
- OpenAlex
- W2093579930
- Cited by
- 240
- References
- 194
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 7 · 2022: 6 · 2021: 18 · 2020: 7 · 2019: 10 · 2018: 8 · 2017: 12 · 2016: 10 · 2015: 16 · 2014: 25 · 2013: 25 · 2012: 20
- FWCI
- 5.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Growth Factors (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Health and Medical Research Council
- National Medical Research Council
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- ribosome biogenesis, ribosome function, S6K, S6K1, mTOR signaling, 4E-BP1, cell growth regulation, protein synthesis, nutrient signaling, growth factor signaling, PI3K/Akt signaling, signaling crosstalk, cancer
- MeSH terms
- Protein Kinases, Ribosomes, RNA, Ribosomal, Protein Biosynthesis, Signal Transduction, Phosphatidylinositol 3-Kinases, Ribosomal Protein S6 Kinases, Cell Growth Processes, TOR Serine-Threonine Kinases
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