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Translation Stress Regulates Ribosome Synthesis and Cell Proliferation
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
2018 (English)In: International Journal of Molecular Sciences, ISSN 1422-0067, E-ISSN 1422-0067, Vol. 19, no 12, article id 3757Article, review/survey (Refereed) Published
Abstract [en]

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 PI3K delta-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.

Place, publisher, year, edition, pages
MDPI, 2018. Vol. 19, no 12, article id 3757
Keywords [en]
mRNA translation stress, ribosome biogenesis, oncogene, cell cycle, cell signaling pathway
National Category
Cell Biology Cell and Molecular Biology Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:umu:diva-155978DOI: 10.3390/ijms19123757ISI: 000455323500059PubMedID: 30486342OAI: oai:DiVA.org:umu-155978DiVA, id: diva2:1286658
Funder
Swedish Cancer Society, 160598Swedish Research CouncilAvailable from: 2019-02-07 Created: 2019-02-07 Last updated: 2019-05-10Bibliographically approved

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Fåhraeus, Robin

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