Sirtuin 2 Regulates Protein LactoylLys Modifications

Overview

Journal Chembiochem

Specialty Biochemistry

Date 2021 Mar 16

PMID 33725370

Citations 20

Authors

Erin Q Jennings

Jason D Ray

Christopher J Zerio

Marissa N Trujillo

David M McDonald

Eli Chapman

David A Spiegel

James J Galligan

Affiliations

Soon will be listed here.

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.

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