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Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Tsuchiya, Yugo 
Peak-Chew, Sew Yeu 
Newell, Clare 
Miller-Aidoo, Sheritta 
Mangal, Sriyash 

Abstract

Coenzyme A (CoA) is an obligatory cofactor in all branches of life. CoA and its derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. Abnormal biosynthesis and homeostasis of CoA and its derivatives have been associated with various human pathologies, including cancer, diabetes and neurodegeneration. Using an anti-CoA monoclonal antibody and mass spectrometry, we identified a wide range of cellular proteins which are modified by covalent attachment of CoA to cysteine thiols (CoAlation). We show that protein CoAlation is a reversible post-translational modification that is induced in mammalian cells and tissues by oxidising agents and metabolic stress. Many key cellular enzymes were found to be CoAlated in vitro and in vivo in ways that modified their activities. Our study reveals that protein CoAlation is a widespread post-translational modification which may play an important role in redox regulation under physiological and pathophysiological conditions.

Description

Keywords

coenzyme A, metabolic and oxidative stress, post-translational modification, proteomics, Animals, Coenzyme A, Cysteine, HEK293 Cells, Hep G2 Cells, Humans, Kidney, Liver, Male, Myocardium, Organ Specificity, Oxidation-Reduction, Oxidative Stress, Protein Processing, Post-Translational, Proteins, Rabbits, Rats, Sprague-Dawley, Sulfhydryl Compounds

Journal Title

Biochem J

Conference Name

Journal ISSN

0264-6021
1470-8728

Volume Title

474

Publisher

Portland Press Ltd.
Sponsorship
Medical Research Council (MC_U105663142)
Biotechnology and Biological Sciences Research Council (BB/J009865/1)
Biotechnology and Biological Sciences Research Council (BB/H002731/1)
Medical Research Council (MC_UU_12012/2)
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (100574/Z/12/Z)
Wellcome Trust (110159/Z/15/Z)
British Heart Foundation (None)
Medical Research Council (MC_PC_12012)