AKT Promotes rRNA Synthesis and Cooperates with c-MYC to Stimulate Ribosome Biogenesis in Cancer

@article{Chan2011AKTPR,
  title={AKT Promotes rRNA Synthesis and Cooperates with c-MYC to Stimulate Ribosome Biogenesis in Cancer},
  author={Joanna C Chan and Katherine M. Hannan and Kim Riddell and Pui Y. Ng and Abigail Peck and Rachel S. Lee and Sandy S. C. Hung and Megan Victoria Astle and Megan Bywater and Meaghan Wall and Gretchen Poortinga and Katarzyna Jastrzebski and Karen E. Sheppard and Brian A. Hemmings and Michael N. Hall and Ricky W. Johnstone and Grant A. McArthur and Ross D. Hannan and Richard B. Pearson},
  journal={Science Signaling},
  year={2011},
  volume={4},
  pages={ra56 - ra56}
}
In addition to promoting translation, AKT also stimulates protein synthesis and cell growth by enhancing ribosome biogenesis. Building the Building Blocks Ribosomes translate mRNA into protein, and the activity of signaling pathways that promote ribosome formation (or biogenesis) is often increased in cancer cells, which have high rates of protein synthesis and cell growth. Thus, each step of ribosome biogenesis can limit cell growth, including the synthesis of ribosomal RNA (rRNA), which… 
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References

SHOWING 1-10 OF 74 REFERENCES
Suppression of Myc oncogenic activity by ribosomal protein haploinsufficiency
TLDR
It is demonstrated that the ability of Myc to increase protein synthesis directly augments cell size and is sufficient to accelerate cell cycle progression independently of known cell cycle targets transcriptionally regulated by Myc, and when protein synthesis is restored to normal levels, Myc-overexpressing precancerous cells are more efficiently eliminated by programmed cell death.
Crosstalk between c‐Myc and ribosome in ribosomal biogenesis and cancer
  • M. Dai, Hua Lu
  • Biology, Medicine
    Journal of cellular biochemistry
  • 2008
TLDR
Some prospects on the interplay between c‐Myc and Ribosomal proteins during ribosomal biogenesis are provided and its implications in cancer are discussed.
Myc-dependent regulation of ribosomal RNA synthesis during Drosophila development
TLDR
It is suggested that during animal development, the control of rRNA synthesis and ribosome biogenesis is an essential Myc function.
Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases
TLDR
Recent advances in understanding the interplay among nutrient availability, transcriptional control and ribosome biogenesis are summarized, with a focus on transcription in response to nutrients.
The role of Myc-induced protein synthesis in cancer.
TLDR
New genetic tools to restore aberrant increases in protein synthesis control are now available, which should enable the dissection of important mechanisms in cancer that rely on the translational machinery.
The RNA polymerase I transcription machinery: an emerging target for the treatment of cancer.
TLDR
Experimental data and potential strategies to downregulate rRNA synthesis and induce an antiproliferative response in cancer cells are discussed.
c-Myc associates with ribosomal DNA and activates RNA polymerase I transcription
TLDR
The results suggest that c-Myc coordinates the activity of all three nuclear RNA polymerases, and thereby plays a key role in regulating ribosome biogenesis and cell growth.
MAD1 and c‐MYC regulate UBF and rDNA transcription during granulocyte differentiation
TLDR
It is shown that granulocytic cells deficient in the c‐MYC antagonist MAD1 display increased cell volume, rDNA transcription and protein synthesis, providing a mechanism for coordination of ribosome biogenesis and cell growth under conditions of sustained growth inhibition such as granulocyte differentiation.
Does the ribosome translate cancer?
TLDR
Although many studies have correlated deregulation of protein biosynthesis with cancer, it remains to be established whether this translates directly into an increase in cancer susceptibility, and under what circumstances.
Growth factor signaling regulates elongation of RNA polymerase I transcription in mammals via UBF phosphorylation and r-chromatin remodeling.
TLDR
ERK phosphorylation of the HMG boxes of UBF, an RNA polymerase I factor essential for transcription enhancement, was shown to directly regulate elongation by inducing the remodeling of ribosomal gene chromatin, suggesting a mechanism for coordinating the cotranscriptional assembly of preribosomal particles.
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