Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways

Yue Chen, Wenhui Zhao, Jeong Soo Yang, Zhongyi Cheng, Hao Luo, Zhike Lu, Minjia Tan, Wei Gu, Yingming Zhao

Research output: Contribution to journalArticlepeer-review

132 Scopus citations

Abstract

Despite of the progress in identifying many Lys acetylation (Kac) proteins, Kac substrates for Kac-regulatory enzymes remain largely unknown, presenting a major knowledge gap in Kac biology. Here we identified and quantified 4623 Kac sites in 1800 Kac proteins in SIRT1+/+ and SIRT1-/- MEF cells, representing the first study to reveal an enzyme-regulated Kac subproteome and the largest Lys acetylome reported to date from a single study. Four hundred eighty-five Kac sites were enhanced by more than 100% after SIRT1 knockout. Our results indicate that SIRT1 regulates the Kac states of diverse cellular pathways. Interestingly, we found that a number of acetyltransferases and major acetyltransferase complexes are targeted by SIRT1. Moreover, we showed that the activities of the acetyltransferases are regulated by SIRT1-mediated deacetylation. Taken together, our results reveal the Lys acetylome in response to SIRT1, provide new insights into mechanisms of SIRT1 function, and offer biomarker candidates for the clinical evaluation of SIRT1-activator compounds.

Original languageEnglish (US)
Pages (from-to)1048-1062
Number of pages15
JournalMolecular and Cellular Proteomics
Volume11
Issue number10
DOIs
StatePublished - Oct 2012

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