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dc.contributor.authorTatham, Michael H.
dc.contributor.authorCole, Christian
dc.contributor.authorScullian, Paul
dc.contributor.authorWilkie, Ross
dc.contributor.authorWestwood, Nicholas J.
dc.contributor.authorStark, Lesley A.
dc.contributor.authorHay, Ronald T.
dc.date.accessioned2016-12-15T17:30:19Z
dc.date.available2016-12-15T17:30:19Z
dc.date.issued2017-02-01
dc.identifier248156542
dc.identifier1223a201-82dd-4401-a774-0836730924b6
dc.identifier85013155822
dc.identifier000393992300014
dc.identifier.citationTatham , M H , Cole , C , Scullian , P , Wilkie , R , Westwood , N J , Stark , L A & Hay , R T 2017 , ' A proteomic approach to analyze the aspirin-mediated lysine acetylome ' , Molecular and Cellular Proteomics , vol. 16 , pp. 310-326 . https://doi.org/10.1074/mcp.O116.065219en
dc.identifier.issn1535-9476
dc.identifier.otherORCID: /0000-0003-0630-0138/work/56424158
dc.identifier.urihttps://hdl.handle.net/10023/9978
dc.descriptionThis work is supported by Cancer Research UK Grant C434/A13067 (M.H.T & R.T.H) and Wellcome Trust Grant 098391/Z/12/7 (R.T.H.).en
dc.description.abstractAspirin, or acetylsalicylic acid is widely used to control pain, inflammation and fever. Important to this function is its ability to irreversibly acetylate cyclooxygenases at active site serines. Aspirin has the potential to acetylate other amino-acid side-chains, leading to the possibility that aspirin-mediated lysine acetylation could explain some of its as-yet unexplained drug actions or side-effects. Using isotopically labeled aspirin-d3, in combination with acetylated lysine purification and LC-MS/MS, we identified over 12000 sites of lysine acetylation from cultured human cells. Although aspirin amplifies endogenous acetylation signals at the majority of detectable endogenous sites, cells tolerate aspirin mediated acetylation very well unless cellular deacetylases are inhibited. Although most endogenous acetylations are amplified by orders of magnitude, lysine acetylation site occupancies remain very low even after high doses of aspirin. This work shows that while aspirin has enormous potential to alter protein function, in the majority of cases aspirin-mediated acetylations do not accumulate to levels likely to elicit biological effects. These findings are consistent with an emerging model for cellular acetylation whereby stoichiometry correlates with biological relevance, and deacetylases act to minimize the biological consequences non-specific chemical acetylations.
dc.format.extent17
dc.format.extent4098282
dc.language.isoeng
dc.relation.ispartofMolecular and Cellular Proteomicsen
dc.subjectAcetylationen
dc.subjectCancer therapeuticsen
dc.subjectChemical biologyen
dc.subjectChemoproteomicsen
dc.subjectDrug targetsen
dc.subjectHistonesen
dc.subjectPost-translational modifications*en
dc.subjectSignal Transductionen
dc.subjectSubstrate identificationen
dc.subjectAspirinen
dc.subjectQD Chemistryen
dc.subjectNDASen
dc.subjectSDG 3 - Good Health and Well-beingen
dc.subject.lccQDen
dc.titleA proteomic approach to analyze the aspirin-mediated lysine acetylomeen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews. School of Chemistryen
dc.contributor.institutionUniversity of St Andrews. EaSTCHEMen
dc.contributor.institutionUniversity of St Andrews. Biomedical Sciences Research Complexen
dc.identifier.doi10.1074/mcp.O116.065219
dc.description.statusPeer revieweden
dc.identifier.urlhttp://www.mcponline.org/content/early/2016/12/02/mcp.O116.065219/suppl/DC1en


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