1521-0081/72/2/486–526$35.00https://doi.org/10.1124/pr.119.018440PHARMACOLOGICALREVIEWSPharmacolRev72:486–526,April2020Copyright©2020byTheAuthor(s)ThisisanopenaccessarticledistributedundertheCCBY-NCAttribution4.0Internationallicense.ASSOCIATEEDITOR:RICHARDD.YETargetingJanusKinasesandSignalTransducerandActivatorofTranscription3toTreatInflammation,Fibrosis,andCancer:Rationale,Progress,andCautionUddalakBharadwaj,1MosesM.Kasembeli,1PremaRobinson,andDavidJ.TweardyDepartmentofInfectiousDiseases,InfectionControl&EmployeeHealth,DivisionofInternalMedicine(U.B.,M.M.K.,P.R.,D.J.T.),andDepartmentofMolecularandCellularOncology(D.J.T.),UniversityofTexas,MDAndersonCancerCenter,Houston,TexasAbstract.....................................................................................488SignificanceStatement......................................................................488I.MolecularandCellularBiologyofJanusKinase/SignalTransducerandActivatorofTranscription3Signaling....................................................................488A.CanonicalJanusKinase/SignalTransducerandActivatorofTranscription3Signaling....4881.JanusKinases.......................................................................4882.SignalTransducerandActivatorofTranscriptionProteins............................4893.NegativeRegulationofCanonicalJanusKinase/SignalTransducerandActivatorofTranscription3Signaling.............................................................4904.Post-TranslationalModificationsofSignalTransducerandActivatorofTranscrip-tion3................................................................................490a.Serine727phosphorylation.......................................................490b.Methylation.......................................................................491c.Acetylation.......................................................................492d.Ubiquitination,ISGylation,andSUMOylation.....................................492B.NoncanonicalSignalTransducerandAc...
