Sirtuin 2 Regulates Protein LactoylLys Modifications

被引：46

作者：

Jennings, Erin Q. ^{[1
]}

Ray, Jason D. ^{[2
]}

Zerio, Christopher J. ^{[1
]}

Trujillo, Marissa N. ^{[1
]}

McDonald, David M. ^{[2
]}

Chapman, Eli ^{[1
]}

Spiegel, David A. ^{[2
]}

Galligan, James J. ^{[1
]}

机构：

[1] Univ Arizona, Coll Pharm, Dept Pharmacol & Toxicol, Tucson, AZ 85721 USA

[2] Yale Univ, Dept Chem, New Haven, CT 06520 USA

来源：

CHEMBIOCHEM | 2021年 / 22卷 / 12期

基金：

美国国家卫生研究院;

关键词：

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

D O I：

10.1002/cbic.202000883

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：2102 / 2106

页数：5

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