Critical protein GAPDH and its regulatory mechanisms in cancer cells

Glyceraldehyde-3-phosphatedehydrogenase(GAPDH),initiallyidentifiedasaglycolyticenzymeandconsideredasahousekeepinggene,iswidelyusedasaninternalcontrolinexperimentsonproteins,mRNA,andDNA.However,emergingevidenceindicatesthatGAPDHisimplicatedindiversefunctionsindependentofitsroleinenergymetabolism;theexpressionstatusofGAPDHisalsoderegulatedinvariouscancercells.OneofthemostcommoneffectsofGAPDHisitsinconsistentroleinthedeterminationofcancercellfate.Furthermore,studieshavedescribedGAPDHasaregulatorofcelldeath;otherstudieshavesuggestedthatGAPDHparticipatesintumorprogressionandservesasanewtherapeutictarget.However,relatedregulatorymechanismsofitsnumerouscellularfunctionsandderegulatedexpressionlevelsremainunclear.GAPDHistightlyregulatedattranscriptionalandposttranscriptionallevels,whichareinvolvedintheregulationofdiverseGAPDHfunctions.Severalcancer-relatedfactors,suchasinsulin,hypoxiainduciblefactor-1(HIF-1),p53,nitricoxide(NO),andacetylatedhistone,notonlymodulateGAPDHgeneexpressionbutalsoaffectproteinfunctionsviacommonpathways.Moreover,posttranslationalmodifications(PTMs)occurringinGAPDHincancercellsresultinnewactivitiesunrelatedtotheoriginalglycolyticfunctionofGAPDH.Inthisreview,recentfindingsrelatedtoGAPDHtranscriptionalregulationandPTMsaresummarized.MechanismsandpathwaysinvolvedinGAPDHregulationanditsdifferentrolesincancercellsarealsodescribed.