Sirtuin 2 Regulates Protein LactoylLys Modifications.

TLDR: In this article, SIRT2 was used as an eraser for post-translational modification (PTM) in the context of CRISPR-Cas9 and it was shown that SIRT 2 controls the abundance of this PTM both globally and on chromatin.

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.