RPS3a Over-Expressed in HBV-Associated Hepatocellular Carcinoma Enhances the HBx-Induced NF-κB Signaling via Its Novel Chaperoning Function 英文参考文献.docVIP
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RPS3a Over-Expressed in HBV-Associated Hepatocellular Carcinoma Enhances the HBx-Induced NF-κB Signaling via Its Novel Chaperoning Function 英文参考文献
RPS3aOver-ExpressedinHBV-AssociatedHepatocellular
CarcinomaEnhancestheHBx-InducedNF-k BSignaling
viaItsNovelChaperoningFunction
Keo-HeunLim1,Kyun-HwanKim2,5*,SeongIlChoi7,Eun-SookPark2,SeungHwaPark4,KisunRyu1 ,Yong
KwangPark2,SoYoungKwon3,Sung-IlYang2,5,HanChuLee6,In-KyungSung3,BaikL.Seong1,7*
1Department of Biotechnology, College of Life science and Biotechnology, Yonsei University, Seoul, Korea, 2Department of Pharmacology, IBST, Konkuk University
SchoolofMedicine,Seoul,Korea,3DepartmentofInternalMedicine,IBST,KonkukUniversitySchoolofMedicine,Seoul,Korea,4DepartmentofAnatomyandCenterfor
CancerResearchandDiagnosticMedicine,IBST,KonkukUniversitySchoolofMedicine,Seoul,Korea,5ResearchInstituteofMedicalSciences,KonkukUniversity,Seoul,
Korea,6DepartmentofInternalMedicine,UniversityofUlsanCollegeofMedicine,AsanMedicalCenter,Seoul,Korea,7TranslationalResearchCenterforProteinFunction
Control,YonseiUniversity,Seoul,Korea
Abstract
HepatitisBvirus(HBV)infectionisoneofthemajorcausesofhepatocellularcarcinoma(HCC)development.HepatitisBvirus
Xprotein(HBx)isknowntoplayakeyroleinthedevelopmentofhepatocellularcarcinoma(HCC).Severalcellularproteins
havebeenreportedtobeover-expressedinHBV-associatedHCCtissues,buttheirroleintheHBV-mediatedoncogenesis
remains largely unknown. Here, we explored the effect of the over-expressed cellular protein, a ribosomal protein S3a
(RPS3a),ontheHBx-inducedNF-kBsignalingasacriticalstepforHCCdevelopment.TheenhancementofHBx-inducedNF-
kB signaling by RPS3a was investigated by its ability to translocate NF-kB (p65) into the nucleus and the knock-down
analysis of RPS3a. Notably, further study revealed that the enhancement of NF-kB by RPS3a is mediated by its novel
chaperoningactivitytowardphysiologicalHBx.Theover-expressionofRPS3asignificantlyincreasedthesolubilityofhighly
aggregation-proneHBx.ThischaperoningfunctionofRPS3aforHBxiscloselycorrelatedwiththeenhancedNF-k Bactivity
byRPS3a.Inaddition,themutationalstudyofRPS3ashowedthatitsN-terminaldomain(1–50
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