Abstract
Abstract Hepatitis B virus (HBV) is strongly associated with the development of hepatocellular carcinoma (HCC). Among the HBV viral proteins, X protein (HBx) is regarded as a major risk factor of HCC. HBx contributes to HCC development through regulating expression of many host or viral genes and interacting with other cellular proteins. In this study, proteins that interact with HBx were analyzed by immunoprecipitation and subsequent LC/MS/MS. We identified 60 HBx interacting proteins that function in a wide spectrum of biology. Among these proteins, we were interested in PARP1, Poly (ADP-ribose) polymerase, a crucial factor in base excision repair (BER) pathway, since HBx was known to inhibit DNA repair capacity in cancer cells. Therefore, we characterized the cross-talk between HBx and PARP-1. HBx and PARP-1 colocalized in the nucleus and they are physically associated. Coimmunoprecipitation experiments revealed that the catalytic domain of PARP-1 bound to HBx. Chromatin immunoprecipitation showed that HBx inhibited the recruitment of DNA damage induced by paraquat treatment. HBx overexpression significantly inhibited the protein expression of the DNA damage response factors that respond to the paraquat-induced oxidative stress. Finally, HBx further enhanced the level of 8-OHdG, the marker of DNA damage, under oxidative stress. Together, these data suggest that the interaction between HBx and PARP1 inhibits DNA repair, which could result in onset of hepatocarcinogenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2120. doi:1538-7445.AM2012-2120
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
