Cells respond to external stress conditions by controlling gene expression, a process which occurs rapidly via post-transcriptional regulation at the level of protein synthesis. Global control of translation is mediated by modification of translation factors to allow reprogramming of the translatome and synthesis of specific proteins that are required for stress protection or initiation of apoptosis. In the present study, we have investigated how global protein synthesis rates are regulated upon mild cooling. We demonstrate that although there are changes to the factors that control initiation, including phosphorylation of eukaryotic translation initiation factor 2 (eIF2) on the α-subunit, the reduction in the global translation rate is mediated by regulation of elongation via phosphorylation of eukaryotic elongation factor 2 (eEF2) by its specific kinase, eEF2K (eukaryotic elongation factor 2 kinase). The AMP/ATP ratio increases following cooling, consistent with a reduction in metabolic rates, giving rise to activation of AMPK (5′-AMP-activated protein kinase), which is upstream of eEF2K. However, our data show that the major trigger for activation of eEF2K upon mild cooling is the release of Ca2+ ions from the endoplasmic reticulum (ER) and, importantly, that it is possible to restore protein synthesis rates in cooled cells by inhibition of this pathway at multiple points. As cooling has both therapeutic and industrial applications, our data provide important new insights into how the cellular responses to this stress are regulated, opening up new possibilities to modulate these responses for medical or industrial use at physiological or cooler temperatures.
Skip Nav Destination
Article navigation
January 2015
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
- PDF Icon PDF LinkEditorial Board
Research Article|
January 06 2015
Eukaryotic elongation factor 2 kinase regulates the cold stress response by slowing translation elongation
John R. P. Knight;
John R. P. Knight
1
*Medical Research Council Toxicology Unit, Lancaster Road, Leicester LE1 9HN, U.K.
Search for other works by this author on:
Amandine Bastide;
Amandine Bastide
1
*Medical Research Council Toxicology Unit, Lancaster Road, Leicester LE1 9HN, U.K.
Search for other works by this author on:
Anne Roobol;
Anne Roobol
†School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, U.K.
Search for other works by this author on:
Jo Roobol;
Jo Roobol
†School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, U.K.
Search for other works by this author on:
Thomas J. Jackson;
Thomas J. Jackson
*Medical Research Council Toxicology Unit, Lancaster Road, Leicester LE1 9HN, U.K.
Search for other works by this author on:
Wahyu Utami;
Wahyu Utami
‡Centre for Analytical Bioscience, School of Pharmacy, University Park, University of Nottingham, Nottingham NG7 2RD, U.K.
Search for other works by this author on:
David A. Barrett;
David A. Barrett
‡Centre for Analytical Bioscience, School of Pharmacy, University Park, University of Nottingham, Nottingham NG7 2RD, U.K.
Search for other works by this author on:
C. Mark Smales;
C. Mark Smales
2
†School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, U.K.
2Correspondence may be addressed to either author (email aew5@le.ac.uk or email c.m.smales@kent.ac.uk).
Search for other works by this author on:
Anne E. Willis
Anne E. Willis
2
*Medical Research Council Toxicology Unit, Lancaster Road, Leicester LE1 9HN, U.K.
2Correspondence may be addressed to either author (email aew5@le.ac.uk or email c.m.smales@kent.ac.uk).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
August 21 2014
Revision Received:
October 23 2014
Accepted:
October 29 2014
Accepted Manuscript online:
October 29 2014
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2015 Biochemical Society
2015
Biochem J (2015) 465 (2): 227–238.
Article history
Received:
August 21 2014
Revision Received:
October 23 2014
Accepted:
October 29 2014
Accepted Manuscript online:
October 29 2014
Citation
John R. P. Knight, Amandine Bastide, Anne Roobol, Jo Roobol, Thomas J. Jackson, Wahyu Utami, David A. Barrett, C. Mark Smales, Anne E. Willis; Eukaryotic elongation factor 2 kinase regulates the cold stress response by slowing translation elongation. Biochem J 15 January 2015; 465 (2): 227–238. doi: https://doi.org/10.1042/BJ20141014
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.