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Article: Pin1 interacts with a specific serine-proline motif in hepatitis B virus X-protein to enhance hepatocarcinogenesis

TitlePin1 interacts with a specific serine-proline motif in hepatitis B virus X-protein to enhance hepatocarcinogenesis
Authors
Issue Date2007
PublisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastro
Citation
Gastroenterology, 2007, v. 132 n. 3, p. 1088-1103 How to Cite?
AbstractBackground & Aims: The peptidyl prolyl isomerase Pin1 frequently is overexpressed in hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) is the most common etiologic agent in HCC, and its encoded X-protein (HBx) is oncogenic and possesses a serine-proline motif that may bind Pin1. The role of Pin1 in hepatocarcinogenesis, particularly in HBV-related HCC, was investigated. Methods: Immunohistochemical staining was performed to evaluate the prevalence of Pin1 overexpression in HCCs of different etiologies. Glutathione S-transferase pull-down and co-immunoprecipitation experiments were used to validate the physical interaction between Pin1 and HBx. Reporter assay, cell proliferation assay, and xenotransplantation experiments were used to show the functional consequence and importance of Pin1-HBx interaction in hepatocarcinogenesis. Results: We showed preferential Pin1 overexpression in HBV-related tumors and confirmed the interaction between Pin1 and HBx at the specific serine-proline motif. Pin1 overexpression increased the protein stability of HBx. Furthermore, HBx-mediated transactivation was enhanced by co-expression of Pin1. HepG2 expressing Pin1 and HBx showed a synergistic increase in cellular proliferation, as compared with cells expressing Pin1 or HBx alone. Furthermore, concomitant expression of Pin1 and HBx in the nontumorigenic human hepatocyte cell line MIHA led to a synergistic increase in tumor growth. Finally, in Hep3B cells with suppressed Pin1 expression, HBx-enhanced tumor growth in nude mice was abrogated. Conclusions: Pin1 binds HBx to enhance hepatocarcinogenesis in HBV-infected hepatocytes. The discovery of an interaction between Pin1 and HBx will further our understanding of the molecular pathogenic mechanism of HBV-related HCC in human beings. © 2007 AGA Institute.
Persistent Identifierhttp://hdl.handle.net/10722/148502
ISSN
2015 Impact Factor: 18.187
2015 SCImago Journal Rankings: 7.170
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPang, Ren_HK
dc.contributor.authorLee, TKWen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorFan, STen_HK
dc.contributor.authorWong, KBen_HK
dc.contributor.authorKwong, Yen_HK
dc.contributor.authorTse, Een_HK
dc.date.accessioned2012-05-29T06:13:21Z-
dc.date.available2012-05-29T06:13:21Z-
dc.date.issued2007en_HK
dc.identifier.citationGastroenterology, 2007, v. 132 n. 3, p. 1088-1103en_HK
dc.identifier.issn0016-5085en_HK
dc.identifier.urihttp://hdl.handle.net/10722/148502-
dc.description.abstractBackground & Aims: The peptidyl prolyl isomerase Pin1 frequently is overexpressed in hepatocellular carcinoma (HCC). Hepatitis B virus (HBV) is the most common etiologic agent in HCC, and its encoded X-protein (HBx) is oncogenic and possesses a serine-proline motif that may bind Pin1. The role of Pin1 in hepatocarcinogenesis, particularly in HBV-related HCC, was investigated. Methods: Immunohistochemical staining was performed to evaluate the prevalence of Pin1 overexpression in HCCs of different etiologies. Glutathione S-transferase pull-down and co-immunoprecipitation experiments were used to validate the physical interaction between Pin1 and HBx. Reporter assay, cell proliferation assay, and xenotransplantation experiments were used to show the functional consequence and importance of Pin1-HBx interaction in hepatocarcinogenesis. Results: We showed preferential Pin1 overexpression in HBV-related tumors and confirmed the interaction between Pin1 and HBx at the specific serine-proline motif. Pin1 overexpression increased the protein stability of HBx. Furthermore, HBx-mediated transactivation was enhanced by co-expression of Pin1. HepG2 expressing Pin1 and HBx showed a synergistic increase in cellular proliferation, as compared with cells expressing Pin1 or HBx alone. Furthermore, concomitant expression of Pin1 and HBx in the nontumorigenic human hepatocyte cell line MIHA led to a synergistic increase in tumor growth. Finally, in Hep3B cells with suppressed Pin1 expression, HBx-enhanced tumor growth in nude mice was abrogated. Conclusions: Pin1 binds HBx to enhance hepatocarcinogenesis in HBV-infected hepatocytes. The discovery of an interaction between Pin1 and HBx will further our understanding of the molecular pathogenic mechanism of HBV-related HCC in human beings. © 2007 AGA Institute.en_HK
dc.languageengen_US
dc.publisherWB Saunders Co. The Journal's web site is located at http://www.elsevier.com/locate/gastroen_HK
dc.relation.ispartofGastroenterologyen_HK
dc.subject.meshAmino Acid Motifsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshCarcinoma, Hepatocellular - Genetics - Metabolism - Pathology - Virologyen_US
dc.subject.meshCell Line, Tumoren_US
dc.subject.meshCell Proliferationen_US
dc.subject.meshCell Transformation, Neoplastic - Genetics - Metabolismen_US
dc.subject.meshHepatitis B - Complications - Genetics - Metabolism - Pathology - Virologyen_US
dc.subject.meshHumansen_US
dc.subject.meshLiver Neoplasms - Genetics - Metabolism - Pathology - Virologyen_US
dc.subject.meshLiver Neoplasms, Experimental - Metabolism - Pathology - Virologyen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Nudeen_US
dc.subject.meshPeptidylprolyl Isomerase - Genetics - Metabolismen_US
dc.subject.meshPhosphorylationen_US
dc.subject.meshProlineen_US
dc.subject.meshProtein Bindingen_US
dc.subject.meshProto-Oncogene Proteins C-Myc - Genetics - Metabolismen_US
dc.subject.meshRna, Messenger - Metabolismen_US
dc.subject.meshReproducibility Of Resultsen_US
dc.subject.meshSerineen_US
dc.subject.meshTrans-Activators - Genetics - Metabolismen_US
dc.subject.meshTranscription Factor Rela - Genetics - Metabolismen_US
dc.subject.meshTranscription, Geneticen_US
dc.subject.meshTranscriptional Activationen_US
dc.subject.meshTransfectionen_US
dc.subject.meshTransplantation, Heterologousen_US
dc.subject.meshUp-Regulationen_US
dc.subject.meshBcl-X Protein - Genetics - Metabolismen_US
dc.titlePin1 interacts with a specific serine-proline motif in hepatitis B virus X-protein to enhance hepatocarcinogenesisen_HK
dc.typeArticleen_HK
dc.identifier.emailPang, R: robertap@hku.hken_HK
dc.identifier.emailLee, TKW: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailFan, ST: stfan@hku.hken_HK
dc.identifier.emailKwong, Y: ylkwong@hku.hken_HK
dc.identifier.emailTse, E: ewctse@hku.hken_HK
dc.identifier.authorityPang, R=rp00274en_HK
dc.identifier.authorityLee, TKW=rp00447en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityFan, ST=rp00355en_HK
dc.identifier.authorityKwong, Y=rp00358en_HK
dc.identifier.authorityTse, E=rp00471en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1053/j.gastro.2006.12.030en_HK
dc.identifier.pmid17383430en_HK
dc.identifier.scopuseid_2-s2.0-33947303068en_HK
dc.identifier.hkuros126587-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-33947303068&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume132en_HK
dc.identifier.issue3en_HK
dc.identifier.spage1088en_HK
dc.identifier.epage1103en_HK
dc.identifier.eissn1528-0012-
dc.identifier.isiWOS:000245182300031-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridPang, R=7004376659en_HK
dc.identifier.scopusauthoridLee, TKW=7501439435en_HK
dc.identifier.scopusauthoridPoon, RTP=7103097223en_HK
dc.identifier.scopusauthoridFan, ST=7402678224en_HK
dc.identifier.scopusauthoridWong, KB=37096553200en_HK
dc.identifier.scopusauthoridKwong, Y=7102818954en_HK
dc.identifier.scopusauthoridTse, E=7005019454en_HK

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