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Regulation of global protein translation and protein degradation in aerobic dormancy

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Abstract

We hypothesized that protein turnover would be substantially suppressed during estivation in the land snail, Otala lactea, as part of a wholesale move to conserve ATP in the hypometabolic state, and that decreased rates of protein synthesis and degradation would be mediated by altering the phosphorylation state of key proteins. Rates of protein translation, measured in vitro, decreased by ~80% in extracts of foot muscle and hepatopancreas after 2 days of estivation, and this reduction was associated with strong increases in the phosphorylation of ribosomal factors, eIF2α and eEF2, as well as decreased phosphorylation of 4E-BP1. Reductions in levels of markers of ribosomal biogenesis and a tissue-specific reduction in the phosphorylation state of eIF4E and eIF4GI were also evident after 14 days of estivation. Activity of the 20S proteasome decreased by 60–80% after 2 days of estivation and this decrease was mediated by protein kinase G in vitro, whereas protein phosphatase 2A activated the proteasome. Levels of protein carbonyls did not change in snail tissues during estivation whereas the expression heat shock proteins increased, suggesting that protein resistance to damage is enhanced in estivation. In conclusion, protein synthesis and degradation rates were coordinately suppressed during estivation in O. lactea and this is associated with the phosphorylation of ribosomal initiation and elongation factors and the 20S proteasome.

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Abbreviations

eIF:

Eukaryotic initiation factor

eEF:

Eukaryotic elongation factor

P70S6K:

70 kDa protein kinase of ribosomal S6 protein

4E-BP1:

Binding protein-1 of eIF4E

20S, MCP:

Multicatalytic proteasome

mTOR:

Mammalian target of rapamycin

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Acknowledgments

Thanks to J. M. Storey for editorial comment on the manuscript. The research was supported by a discovery grant from the Natural Sciences and Engineering Research Council of Canada (OPG 6793) to K.B.S., by an NSERC postgraduate scholarship to C.J.R. and by NSERC USRA scholarships to MEA and AGG.

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Authors and Affiliations

  1. Department of Molecular Physiology, Vanderbilt University School of Medicine, 710 Robinson Research Building, 2200 Pierce Avenue, Nashville, TN, 37232, USA

    Christopher J. Ramnanan

  2. Department of Biology, Carleton University, 1125 Colonel By Drive, Ottawa, ON, Canada, K1S 5B6

    Marcus E. Allan, Amy G. Groom & Kenneth B. Storey

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  1. Christopher J. Ramnanan
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  2. Marcus E. Allan
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Correspondence to Christopher J. Ramnanan.

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Ramnanan, C.J., Allan, M.E., Groom, A.G. et al. Regulation of global protein translation and protein degradation in aerobic dormancy. Mol Cell Biochem 323, 9–20 (2009). https://doi.org/10.1007/s11010-008-9959-2

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  • DOI: https://doi.org/10.1007/s11010-008-9959-2

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