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Translation Stress Regulates Ribosome Synthesis and Cell Proliferation

1
Inserm UMRS1162, Institut de Génétique Moléculaire, Université Paris 7, Hôpital St. Louis, F-75010 Paris, France
2
RECAMO, Masaryk Memorial Cancer Institute, Zluty kopec 7, 65653 Brno, Czech Republic
3
Department of Medical Biosciences, Building 6M, Umeå University, 901 85 Umeå, Sweden
4
ICCVS, University of Gdańsk, Science, ul. Wita Stwosza 63, 80-308 Gdańsk, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(12), 3757; https://doi.org/10.3390/ijms19123757
Received: 2 November 2018 / Revised: 23 November 2018 / Accepted: 24 November 2018 / Published: 27 November 2018
(This article belongs to the Special Issue Translational Control)
Ribosome and protein synthesis are major metabolic events that control cellular growth and proliferation. Impairment in ribosome biogenesis pathways and mRNA translation is associated with pathologies such as cancer and developmental disorders. Processes that control global protein synthesis are tightly regulated at different levels by numerous factors and linked with multiple cellular signaling pathways. Several of these merge on the growth promoting factor c-Myc, which induces ribosome biogenesis by stimulating Pol I, Pol II, and Pol III transcription. However, how cells sense and respond to mRNA translation stress is not well understood. It was more recently shown that mRNA translation stress activates c-Myc, through a specific induction of E2F1 synthesis via a PI3Kδ-dependent pathway. This review focuses on how this novel feedback pathway stimulates cellular growth and proliferation pathways to synchronize protein synthesis with ribosome biogenesis. It also describes for the first time the oncogenic activity of the mRNA, and not the encoded protein. View Full-Text
Keywords: mRNA translation stress; ribosome biogenesis; oncogene; cell cycle; cell signaling pathway mRNA translation stress; ribosome biogenesis; oncogene; cell cycle; cell signaling pathway
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MDPI and ACS Style

Vadivel Gnanasundram, S.; Fåhraeus, R. Translation Stress Regulates Ribosome Synthesis and Cell Proliferation. Int. J. Mol. Sci. 2018, 19, 3757.

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