Precisecontrolofproteinfunctionisessentialfortheorganizationandfunctionofbiologicalsystems.Amongdifferentregulatoryprocesses,reversiblepost-translationalmodifications(PTMs)provideanelegantmechanismtogovernproteinfunction.AkeyadvantageofPTMsisthattheycanbedynamicallyregulatedatamuchfasterrateandwithalowerenergycostthanproteinturnover.EukaryoticproteomescontainhundredsofdifferenttypesofPTM;however,onlyafewofthem,suchasphosphorylation,glycosylation,methylation,acetylation,ubiquitylationandsumoylation,havebeenstudiedextensively.AlthoughthephysiologicalimportanceofPTMshasbeenknownformorethanhalfacentury,thewide-spreadoccurrenceofPTMsonlystartedtobecomeclearinthefirstyearsofthe21stcentury,whenadvancesinhigh-resolutionmassspectrometryenableddetectionofthousandsoflow-abundancePTMsites1.ItisalsoincreasinglyappreciatedthatcombinationsofPTMscangeneratedistinctproteinisoformswithvaryingfunctions,whichvastlyexpandthefunctionaldiversityofmammalianproteomes2.LysineacetylationisanevolutionarilyconservedPTMoccurringinbothprokaryotesandeukaryotes.AcetylationwasfirstdiscoveredonhistonesbyVincentAllfreyandcolleaguesin1964(ref.3).Subsequently,acetylationwasfoundonhigh-mobilitygroup(HMG)proteins4,whicharechromatin-bindingnon-histoneproteins,andontubulin5.Inthemid-1990stolate1990s,acetylationofthetranscriptionfactorp53wasdiscovered,thefirstmam-malianhistoneacetyltransferases(HATs)andhistonedeacetylases(HDACs)wereidentified,thebromodomainwasidentifiedasanacetyl-lysinereaderdomain,andpotentdeacetylaseinhibitorswerediscovered(reviewedelsewhere6).Thesegroundbreakingdiscoveriessetthestageforthefieldofnon-histoneproteinacetylation.Wewishtoclarifythatthetermacetylationcanencompassothertypesofproteinacetylation,suchasamino-terminalproteinacetylationandO-linkedacetylationofserineandthreonine.Unlessotherwisespecified,inthisReview,acetylationrefersonlytoNε-lysineacetylation.Overthepastdecade,advancesinmassspectrometry-basedproteomicshavevastlyexpandedthecatalogueofendogenouslyacetylatedproteins,...
