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Sci. Signal., 5 June 2012
Vol. 5, Issue 227, p. pe25
[DOI: 10.1126/scisignal.2003163]

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F-Box Proteins Elongate Translation During Stress Recovery

Sylvain Meloche1,2* and Philippe P. Roux1,3*

1 Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
2 Department of Pharmacology, Faculty of Medicine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.
3 Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montreal, Quebec H3C 3J7, Canada.

Abstract: Protein synthesis is energetically costly and is tightly regulated by evolutionarily conserved mechanisms. Under restrictive growth conditions and in response to various stresses, such as DNA damage, cells inhibit protein synthesis to redirect available adenosine triphosphate to more essential processes. Conversely, proliferating cells, such as cancer cells, increase protein synthetic rates to support growth-related anabolic processes. mRNA translation occurs in three separate phases, consisting of initiation, elongation, and termination. Although all three phases are highly regulated, most of the translational control occurs at the rate-limiting initiation step. New evidence has described a molecular mechanism involved in the regulation of translation elongation. DNA damage initially slowed down elongation rates by activating the eukaryotic elongation factor 2 kinase (eEF2K) through an adenosine monophosphate (AMP)–activated protein kinase (AMPK)–dependent mechanism. However, during checkpoint recovery, the SCF (Skp, Cullin, F-box–containing) βTrCP (β-transducin repeat–containing protein) E3 ubiquitin ligase promoted degradation of eEF2K, thereby allowing the restoration of peptide chain elongation. These findings establish an important link between DNA damage signaling and the regulation of translation elongation.

* Corresponding author. E-mail: sylvain.meloche{at}umontreal.ca (S.M.); philippe.roux{at}umontreal.ca (P.P.R.)

Citation: S. Meloche, P. P. Roux, F-Box Proteins Elongate Translation During Stress Recovery. Sci. Signal. 5, pe25 (2012).

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