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

نویسندگان

  • Yugo Tsuchiya
  • Sew Yeu Peak-Chew
  • Clare Newell
  • Sheritta Miller-Aidoo
  • Sriyash Mangal
  • Alexander Zhyvoloup
  • Jovana Bakovic´
  • Oksana Malanchuk
  • Gonçalo C. Pereira
  • Vassilios Kotiadis
  • Gyorgy Szabadkai
  • Michael R. Duchen
  • Mark Campbell
  • Sergio Rodriguez Cuenca
  • Antonio Vidal-Puig
  • Andrew M. James
  • Michael P. Murphy
  • Valeriy Filonenko
  • Mark Skehel
  • Ivan Gout
چکیده

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.

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عنوان ژورنال:

دوره 474  شماره 

صفحات  -

تاریخ انتشار 2017