Seeonlineversionforlegendandreferences.930Cell133,May30,2008©2008ElsevierInc.DOI10.1016/j.cell.2008.05.020SnapShot:p53PosttranslationalModificationsJan-PhilippKruseandWeiGuInstituteforCancerGeneticsandDepartmentofPathologyandCellBiology,ColumbiaUniversity,NewYork,NewYork,USASiteModifyingEnzymeCellularFunctionDiseaseorKnockoutPhenotypePhosphorylationN-Terminal:S6,S9,S15,T18,S20ATM,DNAPK,•CK1ERKs,ATR,p38•kinase,mTOR,Chk1/Chk2,JNK,MAPKAP2,Hipk4ActivatedbyDNAdamage,UVlight,ionizingradiation,replicativesenes-•cence,orphosphatidylcholines.N-terminalphosphorylationcausesp53stabilizationbyinhibitingthep53-•MDM2interaction.KnockinmicecarryingseparateanalogstohumanSer18/•Ser23mutationarephenotypicallynormal.ThymocytesfromSer18mutantmicearesusceptibletoionizingradiation-inducedapoptosis,whereasS23mutationinEScellsandMEFsisdispensableforp53stabilizationandactivation.Ser18/Ser23doublemutantknockinmicedis-playreducedapoptosisinthymocytesanddevelopsomemalignancies.Veryraremutationsreportedinhumantumors.•S33,S37,S36,S46,T55,T81GSK3•β,p38kinase,ATR,DNAPK,JNK,AMPKalphaHIPK2,DYKR2,•ERK2,TAF1ActivationbyUVlight(S33,S37,S46,Thr81),H•2O2treatment(S33),γ-radiation,DNAdamage(S37),andglucosedeprivation(Ser46).Phosphorylationleadstostabilizationandpromotesp53transcriptional•activitytoregulatep53-mediatedcell-cyclearrestandapoptosis.Veryraremutationsreportedinhumantumors.•S149,T150,T155CSN-associated•kinasecomplexActivatedinunstressedcells.•Promotesp53degradation.•Veryraremutationsreportedinhumantumors.•S315,S376,S378,S392PKC,PKR,•GSK3βFACT-CK2,p38•kinaseCDK(cdc2/ck2),•AURKAActivatedbyUVlight(CDK/GSK3•β,FACT-CK2,p38kinase),AURKAover-expression,andinterferonsignaling(PKR)S351phosphorylationactivatesp53-mediatedtranscriptiontoregulate•apoptosisandcellcycle.PKCconstitutivelyphosphorylatesp53atS376andS378inunstressed•cells,IRstressleadstodephosphorylation.S392phosphorylationpromotessequence-specificp53DNAbinding.•KnockinofS392mouseanalog(S389)isphenotypically•normal...
