Sirtuin 2 Regulates Protein LactoylLys Modifications

Erin Q. Jennings, Jason D. Ray, Christopher J. Zerio, Marissa N. Trujillo, David M. McDonald, Eli Chapman, David A. Spiegel, James J. Galligan

Research output: Contribution to journalArticlepeer-review

Abstract

Post-translational modifications (PTMs) play roles in both physiological and pathophysiological processes through the regulation of enzyme structure and function. We recently identified a novel PTM, lactoylLys, derived through a nonenzymatic mechanism from the glycolytic by-product, lactoylglutathione. Under physiologic scenarios, glyoxalase 2 prevents the accumulation of lactoylglutathione and thus lactoylLys modifications. What dictates the site-specificity and abundance of lactoylLys PTMs, however, remains unknown. Here, we report sirtuin 2 as a lactoylLys eraser. Using chemical biology and CRISPR-Cas9, we show that SIRT2 controls the abundance of this PTM both globally and on chromatin. These results address a major gap in our understanding of how nonenzymatic PTMs are regulated and controlled.

Original languageEnglish (US)
JournalChemBioChem
DOIs
StateAccepted/In press - 2021

Keywords

  • lactoylLys
  • molecular modeling
  • post-translational modification
  • protein modification
  • sirtuin

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Organic Chemistry

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