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Sci. Signal., 5 June 2012
Vol. 5, Issue 227, p. ra40
[DOI: 10.1126/scisignal.2002718]

RESEARCH ARTICLES

Editor's Summary

Activated, Then Degraded, Stop-Start Regulation of Protein Synthesis
A key step in the process of translating mRNA into protein is the repositioning of the mRNA in the ribosome to enable elongation of the polypeptide chain. mRNA translocation in the ribosome is mediated by eukaryotic elongation factor 2 (eEF2), which is inhibited when phosphorylated by eEF2 kinase (eEF2K). Because protein synthesis is energetically costly, stressed cells inhibit this process to devote resources to stress responses. Kruiswijk et al. investigated the mechanisms by which genotoxic stress results in inhibition of protein synthesis. In response to a DNA-damaging agent, eEF2K was phosphorylated and activated by the kinase AMPK, thus leading to inhibition of eEF2 and a slowdown in elongation translation. eEF2K subsequently autophosphorylated itself in a motif recognized by the E3 ubiquitin ligase SCFβTrCP, and the resulting degradation of eEF2K enabled elongation translation to resume. Thus, the activation and subsequent degradation of eEF2K by genotoxic stress are coupled to inhibition of protein synthesis in response to DNA damage and resumption of protein synthesis after DNA damage has been resolved.

Citation: F. Kruiswijk, L. Yuniati, R. Magliozzi, T. Y. Low, R. Lim, R. Bolder, S. Mohammed, C. G. Proud, A. J. R. Heck, M. Pagano, D. Guardavaccaro, Coupled Activation and Degradation of eEF2K Regulates Protein Synthesis in Response to Genotoxic Stress. Sci. Signal. 5, ra40 (2012).

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Proteasome-dependent Degradation of Transcription Factor Activating Enhancer-binding Protein 4 (TFAP4) Controls Mitotic Division.
S. D'Annibale, J. Kim, R. Magliozzi, T. Y. Low, S. Mohammed, A. J. R. Heck, and D. Guardavaccaro (2014)
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Proteasomal Degradation of Eukaryotic Elongation Factor-2 Kinase (EF2K) Is Regulated by cAMP-PKA Signaling and the SCF{beta}TRCP Ubiquitin E3 Ligase.
S. L. Wiseman, Y. Shimizu, C. Palfrey, and A. C. Nairn (2013)
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F-Box Proteins Elongate Translation During Stress Recovery.
S. Meloche and P. P. Roux (2012)
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