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Lysine glutarylation is a protein posttranslational modification regulated by SIRT5.

Publication ,  Journal Article
Tan, M; Peng, C; Anderson, KA; Chhoy, P; Xie, Z; Dai, L; Park, J; Chen, Y; Huang, H; Zhang, Y; Ro, J; Wagner, GR; Green, MF; Madsen, AS ...
Published in: Cell Metab
April 1, 2014

We report the identification and characterization of a five-carbon protein posttranslational modification (PTM) called lysine glutarylation (Kglu). This protein modification was detected by immunoblot and mass spectrometry (MS), and then comprehensively validated by chemical and biochemical methods. We demonstrated that the previously annotated deacetylase, sirtuin 5 (SIRT5), is a lysine deglutarylase. Proteome-wide analysis identified 683 Kglu sites in 191 proteins and showed that Kglu is highly enriched on metabolic enzymes and mitochondrial proteins. We validated carbamoyl phosphate synthase 1 (CPS1), the rate-limiting enzyme in urea cycle, as a glutarylated protein and demonstrated that CPS1 is targeted by SIRT5 for deglutarylation. We further showed that glutarylation suppresses CPS1 enzymatic activity in cell lines, mice, and a model of glutaric acidemia type I disease, the last of which has elevated glutaric acid and glutaryl-CoA. This study expands the landscape of lysine acyl modifications and increases our understanding of the deacylase SIRT5.

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Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

April 1, 2014

Volume

19

Issue

4

Start / End Page

605 / 617

Location

United States

Related Subject Headings

  • Sirtuins
  • Proteomics
  • Protein Processing, Post-Translational
  • Molecular Structure
  • Models, Biological
  • Mice
  • Mass Spectrometry
  • Lysine
  • Immunoblotting
  • Endocrinology & Metabolism
 

Citation

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Tan, M., Peng, C., Anderson, K. A., Chhoy, P., Xie, Z., Dai, L., … Zhao, Y. (2014). Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab, 19(4), 605–617. https://doi.org/10.1016/j.cmet.2014.03.014
Tan, Minjia, Chao Peng, Kristin A. Anderson, Peter Chhoy, Zhongyu Xie, Lunzhi Dai, Jeongsoon Park, et al. “Lysine glutarylation is a protein posttranslational modification regulated by SIRT5.Cell Metab 19, no. 4 (April 1, 2014): 605–17. https://doi.org/10.1016/j.cmet.2014.03.014.
Tan M, Peng C, Anderson KA, Chhoy P, Xie Z, Dai L, et al. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 2014 Apr 1;19(4):605–17.
Tan, Minjia, et al. “Lysine glutarylation is a protein posttranslational modification regulated by SIRT5.Cell Metab, vol. 19, no. 4, Apr. 2014, pp. 605–17. Pubmed, doi:10.1016/j.cmet.2014.03.014.
Tan M, Peng C, Anderson KA, Chhoy P, Xie Z, Dai L, Park J, Chen Y, Huang H, Zhang Y, Ro J, Wagner GR, Green MF, Madsen AS, Schmiesing J, Peterson BS, Xu G, Ilkayeva OR, Muehlbauer MJ, Braulke T, Mühlhausen C, Backos DS, Olsen CA, McGuire PJ, Pletcher SD, Lombard DB, Hirschey MD, Zhao Y. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 2014 Apr 1;19(4):605–617.
Journal cover image

Published In

Cell Metab

DOI

EISSN

1932-7420

Publication Date

April 1, 2014

Volume

19

Issue

4

Start / End Page

605 / 617

Location

United States

Related Subject Headings

  • Sirtuins
  • Proteomics
  • Protein Processing, Post-Translational
  • Molecular Structure
  • Models, Biological
  • Mice
  • Mass Spectrometry
  • Lysine
  • Immunoblotting
  • Endocrinology & Metabolism