title: Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
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.
authors: Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois 60637, USA.
authors: Yue
authors: Y
authors: Chen
authors: Wenhui
authors: W
authors: Zhao
authors: Jeong Soo
authors: JS
authors: Yang
authors: Zhongyi
authors: Z
authors: Cheng
authors: Hao
authors: H
authors: Luo
authors: Zhike
authors: Z
authors: Lu
authors: Minjia
authors: M
authors: Tan
authors: Wei
authors: W
authors: Gu
authors: Yingming
authors: Y
authors: Zhao
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D017353:Gene Deletion; D007553:Isotope Labeling; D008239:Lysine / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D051379:Mice; D018345:Mice, Knockout; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D000123:Acetyltransferases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D008239:Lysine