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

doi:10.1002/cbic.202000883

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 journal › Article › peer-review

40 Scopus citations

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 language	English (US)
Pages (from-to)	2102-2106
Number of pages	5
Journal	ChemBioChem
Volume	22
Issue number	12
DOIs	https://doi.org/10.1002/cbic.202000883
State	Published - Jun 15 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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10.1002/cbic.202000883

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title = "Sirtuin 2 Regulates Protein LactoylLys Modifications",

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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author = "Jennings, {Erin Q.} and Ray, {Jason D.} and Zerio, {Christopher J.} and Trujillo, {Marissa N.} and McDonald, {David M.} and Eli Chapman and Spiegel, {David A.} and Galligan, {James J.}",

note = "Funding Information: aMGO was a generous gift from Dr. Mogens Johannsen (Aarhus University, Denmark). Financial support was provided by National Institutes of Health Grants (T32 ES007091 for E.Q.J.; 2T32GM06754 3‐17 for J.D.R.; T32 GM008804 for C.J.Z.; NIEHS R01ES031463 for E.C.; R35 GM137910 for J.J.G.) and the ALSAM Skaggs Scholars Program (J.J.G.). Funding Information: aMGO was a generous gift from Dr. Mogens Johannsen (Aarhus University, Denmark). Financial support was provided by National Institutes of Health Grants (T32 ES007091 for E.Q.J.; 2T32GM06754 3-17 for J.D.R.; T32 GM008804 for C.J.Z.; NIEHS R01ES031463 for E.C.; R35 GM137910 for J.J.G.) and the ALSAM Skaggs Scholars Program (J.J.G.). Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",

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month = jun,

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doi = "10.1002/cbic.202000883",

language = "English (US)",

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AU - Jennings, Erin Q.

AU - Ray, Jason D.

AU - Zerio, Christopher J.

AU - Trujillo, Marissa N.

AU - McDonald, David M.

AU - Chapman, Eli

AU - Spiegel, David A.

AU - Galligan, James J.

N1 - Funding Information: aMGO was a generous gift from Dr. Mogens Johannsen (Aarhus University, Denmark). Financial support was provided by National Institutes of Health Grants (T32 ES007091 for E.Q.J.; 2T32GM06754 3‐17 for J.D.R.; T32 GM008804 for C.J.Z.; NIEHS R01ES031463 for E.C.; R35 GM137910 for J.J.G.) and the ALSAM Skaggs Scholars Program (J.J.G.). Funding Information: aMGO was a generous gift from Dr. Mogens Johannsen (Aarhus University, Denmark). Financial support was provided by National Institutes of Health Grants (T32 ES007091 for E.Q.J.; 2T32GM06754 3-17 for J.D.R.; T32 GM008804 for C.J.Z.; NIEHS R01ES031463 for E.C.; R35 GM137910 for J.J.G.) and the ALSAM Skaggs Scholars Program (J.J.G.). Publisher Copyright: © 2021 Wiley-VCH GmbH

PY - 2021/6/15

Y1 - 2021/6/15

N2 - 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.

AB - 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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ER -

Sirtuin 2 Regulates Protein LactoylLys Modifications

Abstract

Keywords

ASJC Scopus subject areas

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