Caspase‐3 cleaved p65 fragment dampens NF‐κB‐mediated anti‐apoptotic transcription by interfering with the p65/RPS3 interaction

摘要

Caspase‐3‐mediatedp65cleavageisbelievedtosuppressnuclearfactor‐kappaB(NF‐κB)‐mediatedanti‐apoptotictransactivationincellsundergoingapoptosis.However,onlyasmallpercentageofp65iscleavedduringapoptosis,notinproportiontothedramaticreductioninNF‐κBtransactivation.Hereweshowthatthep651‐97fragmentgeneratedbyCaspase‐3cleavageinterfereswithribosomalproteinS3(RPS3),anNF‐κB“specifier”subunit,andselectivelyretardsthenucleartranslocationofRPS3,thusdampeningtheRPS3/NF‐κB‐dependentanti‐apoptoticgeneexpression.OurfindingsrevealanovelcellfatedeterminationmechanismtoensurecellsundergoprogramedcelldeaththroughinterferingwithRPS3/NF‐κB‐conferredanti‐apoptotictranscriptionbythefragmentfrompartialp65cleavagebyactivatedCaspase‐3...