Regulation of Interleukin-10 Receptor Ubiquitination and Stability by Beta-TrCP-Containing Ubiquitin E3 Ligase 英文参考文献.docVIP

RegulationofInterleukin-10ReceptorUbiquitination andStabilitybyBeta-TrCP-ContainingUbiquitinE3 Ligase HuiJiang1,YiLu1,LiangYuan1,JianghuaiLiu1,2* 1MOEKeyLaboratoryofModelAnimalsforDiseaseStudy,ModelAnimalResearchCenterofNanjingUniversityandNationalResourceCenterforMutantMice,Nanjing, China,2ZhejiangKeyLabforTechnologyApplicationofModelOrganisms,SchoolofLifeScience,WenzhouMedicalCollege,Wenzhou,China Abstract Interleukin-10(IL-10)initiatespotentanti-inflammatoryeffectsviaactivatingitscellsurfacereceptor,composedofIL-10R1 andIL-10R2subunits.ThelevelofIL-10R1isamajordeterminantofthecells’responsivenesstoIL-10.Here,viaaseriesof biochemical analyses using 293T cells reconstituted with IL-10R1, we identify the latter as a novel substrate of bTrCP- containing ubiquitin E3 ligase. Within the intracellular tail of IL-10R1, a canonical (318DpSGFGpS) and a slightly deviated (369DpSGICLQEP) bTrCP recognition motif can additively recruit bTrCP in a phosphorylation-dependent manner. bTrCP recruitment leads to ubiquitination, endocytosis and degradation of IL-10R1, subsequently reducing the cellular responsiveness to IL-10. Our study uncovers a novel negative regulatory mechanism that may potentially affect IL-10 functionintargetcellsunderphysiologicalorpathologicalconditions. Citation:JiangH,LuY,YuanL,LiuJ(2011)RegulationofInterleukin-10ReceptorUbiquitinationandStabilitybyBeta-TrCP-ContainingUbiquitinE3Ligase.PLoS ONE6(11):e27464.doi:10.1371/journal.pone.0027464 Editor:LaszloBuday,HungarianAcademyofSciences,Hungary ReceivedOctober10,2011;AcceptedOctober17,2011;PublishedNovember8,2011 Copyright: ? 2011 Jiang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited. Funding:ThisworkwassupportedbyNationalNaturalScienceFoundationofChinagrants()ndoJL;andChinese Ministry of Science and Technology