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Conference Paper: Pin1 interacts with a specific Serine-Proline motif of Hepatitis B Virus X protein to enhance human hepatocarcinogenesis

TitlePin1 interacts with a specific Serine-Proline motif of Hepatitis B Virus X protein to enhance human hepatocarcinogenesis
Authors
Issue Date2006
PublisherWiley-Blackwell Publishing Asia.
Citation
The 2006 Shanghai-Hong Kong International Liver Congress, Shanghai, China, 24-28 March 2006. In Journal of Gastroenterology and Hepatology, 2006, v. 21 suppl. S2, p. A78-A79, abstract no. 023 How to Cite?
AbstractWe previously reported that the peptidyl prolyl isomerase (PIN1) is over-expressed in hepatocellular carcinoma (HCC) cases related to hepatitis B virus (HBV), and it plays a functional role in hepatocar-cinogenesis (Pang et al, Oncogene 2004). Hepatitis B virus X protein (HBx), a potent transactivator implicated in HBV-related hepatocar-cinogenesis, has a potential PIN1 binding motif. This study investigated the interaction of PIN1 with HBx and its role in HBV-related hepatocar-cinogenesis. We observed positive correlation of PIN1 and HBx expression (p = 0.024) by immunohistochemistry in HBV-related HCCs. Immunofluorescence microscopy confirmed co-localization of HBx with PIN1 in the nucleus, and co-immuoprecip-itation showed that PIN1 bound to ectopically expressed flag-tagged HBx in Hela cells. GST pull-down assay further validated the binding between the two proteins. Co-transfection of PIN1 and HBx transactivated the NF-AT driven luciferase reporter, with two-fold increase in luciferase activity compared with transfection of HBx alone, or PIN1-HBx mutants with abolition of Ser/Pro residues at the pSer41-Pro motif, which abolished its binding with PIN1. Cell proliferation was markedly increased with stable PIN1-HBx transfectants compared with PIN1-HBx mutant transfectants, stable PIN1 or HBx transfectants alone. Subcutaneous injection of PIN1-HBx transfectants in nude mice resulted in development of larger tumors compared with HBx mutants, PIN1 or HBx transfectants alone. We conclude that PIN1 interacts with a specific Serine-Proline motif of HBx and augments its transactivating activity and oncogenic properties. These findings implicate PIN1 expression as an important step in HBV-related hepatocarcinogenesis and suggest that PIN1 may be a novel molecular target for inhibition of hepatocarcinogenesis.
DescriptionYoung Investigator Session
Persistent Identifierhttp://hdl.handle.net/10722/102091
ISSN
2015 Impact Factor: 3.322
2015 SCImago Journal Rankings: 1.190

 

DC FieldValueLanguage
dc.contributor.authorPang, RWCen_HK
dc.contributor.authorLee, KWen_HK
dc.contributor.authorPoon, RTPen_HK
dc.contributor.authorKwong, YLen_HK
dc.contributor.authorTse, EWCen_HK
dc.date.accessioned2010-09-25T20:16:42Z-
dc.date.available2010-09-25T20:16:42Z-
dc.date.issued2006en_HK
dc.identifier.citationThe 2006 Shanghai-Hong Kong International Liver Congress, Shanghai, China, 24-28 March 2006. In Journal of Gastroenterology and Hepatology, 2006, v. 21 suppl. S2, p. A78-A79, abstract no. 023-
dc.identifier.issn0815-9319-
dc.identifier.urihttp://hdl.handle.net/10722/102091-
dc.descriptionYoung Investigator Session-
dc.description.abstractWe previously reported that the peptidyl prolyl isomerase (PIN1) is over-expressed in hepatocellular carcinoma (HCC) cases related to hepatitis B virus (HBV), and it plays a functional role in hepatocar-cinogenesis (Pang et al, Oncogene 2004). Hepatitis B virus X protein (HBx), a potent transactivator implicated in HBV-related hepatocar-cinogenesis, has a potential PIN1 binding motif. This study investigated the interaction of PIN1 with HBx and its role in HBV-related hepatocar-cinogenesis. We observed positive correlation of PIN1 and HBx expression (p = 0.024) by immunohistochemistry in HBV-related HCCs. Immunofluorescence microscopy confirmed co-localization of HBx with PIN1 in the nucleus, and co-immuoprecip-itation showed that PIN1 bound to ectopically expressed flag-tagged HBx in Hela cells. GST pull-down assay further validated the binding between the two proteins. Co-transfection of PIN1 and HBx transactivated the NF-AT driven luciferase reporter, with two-fold increase in luciferase activity compared with transfection of HBx alone, or PIN1-HBx mutants with abolition of Ser/Pro residues at the pSer41-Pro motif, which abolished its binding with PIN1. Cell proliferation was markedly increased with stable PIN1-HBx transfectants compared with PIN1-HBx mutant transfectants, stable PIN1 or HBx transfectants alone. Subcutaneous injection of PIN1-HBx transfectants in nude mice resulted in development of larger tumors compared with HBx mutants, PIN1 or HBx transfectants alone. We conclude that PIN1 interacts with a specific Serine-Proline motif of HBx and augments its transactivating activity and oncogenic properties. These findings implicate PIN1 expression as an important step in HBV-related hepatocarcinogenesis and suggest that PIN1 may be a novel molecular target for inhibition of hepatocarcinogenesis.-
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Asia.-
dc.relation.ispartofJournal of Gastroenterology and Hepatologyen_HK
dc.rightsJournal of Gastroenterology and Hepatology, Right © Wiley-Blackwell Publishing Asia.-
dc.titlePin1 interacts with a specific Serine-Proline motif of Hepatitis B Virus X protein to enhance human hepatocarcinogenesisen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailPang, RWC: robertap@hku.hken_HK
dc.identifier.emailLee, KW: tkwlee@hkucc.hku.hken_HK
dc.identifier.emailPoon, RTP: poontp@hkucc.hku.hken_HK
dc.identifier.emailKwong, YL: ylkwong@hku.hken_HK
dc.identifier.emailTse, EWC: ewctse@hku.hken_HK
dc.identifier.authorityLee, KW=rp00447en_HK
dc.identifier.authorityPoon, RTP=rp00446en_HK
dc.identifier.authorityKwong, YL=rp00358en_HK
dc.identifier.authorityTse, EWC=rp00471en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1440-1746.2006.04402.x-
dc.identifier.hkuros150915en_HK
dc.identifier.volume21-
dc.identifier.issuesuppl. S2-
dc.identifier.spageA78, abstract no. 023-
dc.identifier.epageA79-
dc.publisher.placeAustralia-

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