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Science China Life Sciences

, Volume 62, Issue 11, pp 1514–1520 | Cite as

Profiling of lysine-acetylated proteins in human urine

  • Weiwei Qin
  • Ting Wang
  • He Huang
  • Youhe GaoEmail author
Research Paper

Abstract

A biomarker is a measurable indicator associated with changes in physiological state or disease. In contrast to the blood which is under homeostatic controls, urine reflects changes in the body earlier and more sensitively, and is therefore a better biomarker source. Lysine acetylation is an abundant and highly regulated post-translational modification. It plays a pivotal role in modulating diverse biological processes and is associated with various important diseases. Enrichment or visualization of proteins with specific post-translational modifications provides a method for sampling the urinary proteome and reducing sample complexity. In this study, we used anti-acetyllysine antibody-based immunoaffinity enrichment combined with high-resolution mass spectrometry to profile lysine-acetylated proteins in normal human urine. A total of 629 acetylation sites on 315 proteins were identified, including some very low-abundance proteins. This is the first proteome-wide characterization of lysine acetylation proteins in normal human urine. Our dataset provides a useful resource for the further discovery of lysine-acetylated proteins as biomarkers in urine.

Keywords

urine post-translational modification lysine acetylation 

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Notes

Acknowledgements

This work was supported by the National Key Research and Development Program of China (2018YFC0910202, 2016YFC1306300), the Beijing Natural Science Foundation (7172076), the Beijing cooperative construction project (110651103), the Beijing Normal University (11100704), the Peking Union Medical College Hospital (2016-2.27).

Supplementary material

11427_2017_9367_MOESM1_ESM.docx (281 kb)
Supplementary material, approximately 284 KB.

References

  1. Chou, M.F., and Schwartz, D. (2011). Biological sequence motif discovery using motif–x. Curr Protoc Bioinformatics Chapter 13, Unit 13, 15–24.Google Scholar
  2. Choudhary, C., Kumar, C., Gnad, F., Nielsen, M.L., Rehman, M., Walther, T.C., Olsen, J.V., and Mann, M. (2009). Lysine acetylation targets protein complexes and co–regulates major cellular functions. Science 325, 834–840.CrossRefGoogle Scholar
  3. Decramer, S., Gonzalez de Peredo, A., Breuil, B., Mischak, H., Monsarrat, B., Bascands, J.L., and Schanstra, J.P. (2008). Urine in clinical proteomics. Mol Cell Proteom 7, 1850–1862.CrossRefGoogle Scholar
  4. Gao, Y.H. (2013). Urine—an untapped goldmine for biomarker discovery? Sci China Life Sci 56, 1145–1146.CrossRefGoogle Scholar
  5. Gu, W., and Roeder, R.G. (1997). Activation of p53 sequence–specific DNA binding by acetylation of the p53 C–terminal domain. Cell 90, 595–606.CrossRefGoogle Scholar
  6. Jia, L.L., Liu, X.J., Liu, L., Li, M.X., and Gao, Y.H. (2014). Urimem, a membrane that can store urinary proteins simply and economically, makes the large–scale storage of clinical samples possible. Sci China Life Sci 57, 336–339.CrossRefGoogle Scholar
  7. Kim, S.C., Sprung, R., Chen, Y., Xu, Y., Ball, H., Pei, J., Cheng, T., Kho, Y., Xiao, H., Xiao, L., et al. (2006). Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 23, 607–618.CrossRefGoogle Scholar
  8. Li, M.L., Zhao, M.D., and Gao, Y.H. (2014). Changes of proteins induced by anticoagulants can be more sensitively detected in urine than in plasma. Sci China Life Sci 57, 649–656.CrossRefGoogle Scholar
  9. Li, Q.R., Fan, K.X., Li, R.X., Dai, J., Wu, C.C., Zhao, S.L., Wu, J.R., Shieh, C.H., and Zeng, R. (2010). A comprehensive and nonprefractionation on the protein level approach for the human urinary proteome: touching phosphorylation in urine. Rapid Commun Mass Sp 24, 823–832.CrossRefGoogle Scholar
  10. Mann, M., and Jensen, O.N. (2003). Proteomic analysis of posttranslational modifications. Nat Biotechnol 21, 255–261.CrossRefGoogle Scholar
  11. Marimuthu, A., O'Meally, R.N., Chaerkady, R., Subbannayya, Y., Nanjappa, V., Kumar, P., Kelkar, D.S., Pinto, S.M., Sharma, R., Renuse, S., et al. (2011). A comprehensive map of the human urinary proteome. J Proteome Res 10, 2734–2743.CrossRefGoogle Scholar
  12. Menzies, K.J., Zhang, H., Katsyuba, E., and Auwerx, J. (2016). Protein acetylation in metabolism—metabolites and cofactors. Nat Rev Endocrinol 12, 43–60.CrossRefGoogle Scholar
  13. Olsen, J.V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., and Mann, M. (2006). Global, in vivo, and site–specific phosphorylation dynamics in signaling networks. Cell 127, 635–648.CrossRefGoogle Scholar
  14. Petersen, B., Petersen, T.N., Andersen, P., Nielsen, M., and Lundegaard, C. (2009). A generic method for assignment of reliability scores applied to solvent accessibility predictions. BMC Struct Biol 9, 51.CrossRefGoogle Scholar
  15. Pons, D., de Vries, F.R., van den Elsen, P.J., Heijmans, B.T., Quax, P.H.A., and Jukema, J.W. (2009). Epigenetic histone acetylation modifiers in vascular remodelling: new targets for therapy in cardiovascular disease. Eur Heart J 30, 266–277.CrossRefGoogle Scholar
  16. Rotilio, D., Della Corte, A., D’Imperio, M., Coletta, W., Marcone, S., Silvestri, C., Giordano, L., Di Michele, M., and Donati, M.B. (2012). Proteomics: bases for protein complexity understanding. Thrombosis Res 129, 257–262.CrossRefGoogle Scholar
  17. Vidali, G., Gershey, E.L., and Allfrey, V.G. (1968). Chemical studies of histone acetylation the distribution of εN–acetyllysine in calf thymus histones. J Biol Chem 243, 6361–6366.PubMedGoogle Scholar
  18. Voelter–Mahlknecht, S. (2016). Epigenetic associations in relation to cardiovascular prevention and therapeutics. Clin Epigenet 8, 4.CrossRefGoogle Scholar
  19. Wang, L., Li, F., Sun, W., Wu, S., Wang, X., Zhang, L., Zheng, D., Wang, J., and Gao, Y. (2006). Concanavalin A–captured glycoproteins in healthy human urine. Mol Cell Proteom 5, 560–562.CrossRefGoogle Scholar
  20. Wang, Q., Zhang, Y., Yang, C., Xiong, H., Lin, Y., Yao, J., Li, H., Xie, L., Zhao, W., Yao, Y., et al. (2010). Acetylation of metabolic enzymes coordinates carbon source utilization and metabolic flux. Science 327, 1004–1007.CrossRefGoogle Scholar
  21. Yu, W., Lin, Y., Yao, J., Huang, W., Lei, Q., Xiong, Y., Zhao, S., and Guan, K.L. (2009). Lysine 88 acetylation negatively regulates ornithine carbamoyltransferase activity in response to nutrient signals. J Biol Chem 284, 13669–13675.CrossRefGoogle Scholar
  22. Zhang, F., Cheng, X., Yuan, Y., Wu, J., and Gao, Y. (2015). Urinary microRNA can be concentrated, dried on membranes and stored at room temperature in vacuum bags. PeerJ 3, e1082.CrossRefGoogle Scholar
  23. Zhang, J., Sprung, R., Pei, J., Tan, X., Kim, S., Zhu, H., Liu, C.F., Grishin, N.V., and Zhao, Y. (2009). Lysine acetylation is a highly abundant and evolutionarily conserved modification inEscherichia Coli. Mol Cell Proteom 8, 215–225.CrossRefGoogle Scholar
  24. Zhang, P., Na, H., Liu, Z., Zhang, S., Xue, P., Chen, Y., Pu, J., Peng, G., Huang, X., Yang, F., et al. (2012). Proteomic study and marker protein identification of Caenorhabditis elegans lipid droplets. Mol Cell Proteom 11, 317–328.CrossRefGoogle Scholar
  25. Zhao, M., Li, M., Yang, Y., Guo, Z., Sun, Y., Shao, C., Li, M., Sun, W., and Gao, Y. (2017). A comprehensive analysis and annotation of human normal urinary proteome. Sci Rep 7, 3024.CrossRefGoogle Scholar
  26. Zhao, S., Xu, W., Jiang, W., Yu, W., Lin, Y., Zhang, T., Yao, J., Zhou, L., Zeng, Y., Li, H., et al. (2010). Regulation of cellular metabolism by protein lysine acetylation. Science 327, 1000–1004.CrossRefGoogle Scholar
  27. Zhu, X., Liu, X., Cheng, Z., Zhu, J., Xu, L., Wang, F., Qi, W., Yan, J., Liu, N., Sun, Z., et al. (2016). Quantitative analysis of global proteome and lysine acetylome reveal the differential impacts of VPA and SAHA on HL60 cells. Sci Rep 6, 19926.CrossRefGoogle Scholar

Copyright information

© Science China Press and Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular Biology, Gene Engineering Drug and Biotechnology Beijing Key LaboratoryBeijing Normal UniversityBeijingChina
  2. 2.Department of AnesthesiologyQingdao Municipal HospitalQingdaoChina

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