title: Interactome map reveals phospholipid scramblase 1 as a novel regulator of hepatitis B virus x protein.
abstract: HBV X protein plays crucial roles during viral infection and hepatocellular carcinoma (HCC) development through interaction with various host factors. Here, we mapped the interactome of HBx using a yeast two-hybrid screen. Nine human proteins were identified as novel interacting partners of HBx, one of which is phospholipid scramblase 1 (PLSCR1). PLSCR1 is an interferon-inducible protein that mediates antiviral activity against DNA and RNA viruses. However, the molecular mechanisms of PLSCR1 activity against HBV remain unclear. Here, we reported that PLSCR1 promotes HBx degradation by a proteasome- and ubiquitin-dependent mechanism. Furthermore, we found that PLSCR1 inhibits HBx-mediated cell proliferation. After HBV infection, the protein level of PLSCR1 in plasma is elevated, and chronic hepatitis B patients with low plasma levels of PLSCR1 have a high risk of developing HCC. These results suggest that the nuclear trafficking of PLSCR1 mediates the antiviral activity and anticarcinogenesis against HBV by regulating HBx stability.
authors.affiliation: State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine , Beijing 102206, China.
authors.forename: Yanzhi
authors.initials: Y
authors.lastname: Yuan
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tian
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Gong
authors.forename: Limin
authors.initials: L
authors.lastname: Shang
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chaozhi
authors.initials: C
authors.lastname: Jin
authors.forename: Fuchu
authors.initials: F
authors.lastname: He
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000201:enzymology / Q000821:virology; D016022:Case-Control Studies; D049109:Cell Proliferation; D057809:HEK293 Cells; D056945:Hep G2 Cells; D019694:Hepatitis B, Chronic / Q000097:blood / Q000201:enzymology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008113:Liver Neoplasms / Q000097:blood / Q000201:enzymology / Q000821:virology; D049294:Phospholipid Transfer Proteins / Q000502:physiology*; D060066:Protein Interaction Maps; D055550:Protein Stability; D059748:Proteolysis; D015534:Trans-Activators / Q000378:metabolism*; D054875:Ubiquitination; D054334:Viral Regulatory and Accessory Proteins
chemical_list: C493422:PLSCR1 protein, human; D049294:Phospholipid Transfer Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: HBx; PLSCR1; degradation; hepatitis B virus; ubiquitination; yeast two-hybrid