title: Interaction of the hepatitis B virus X protein (HBx) with heat shock protein 60 enhances HBx-mediated apoptosis.
abstract: Understanding the function of the hepatitis B virus X protein (HBx) is fundamental to elucidating the underlying mechanisms of hepatitis and hepatocarcinogenesis caused by hepatitis B virus (HBV) infection. We identified heat shock protein 60 (Hsp60) as a novel cellular target of HBx by the combination of affinity purification and mass spectrometry. Physical interaction between HBx and Hsp60 was confirmed by standard immunoprecipitation and immunoblot methods. Analysis of HBx deletion constructs showed that amino acids 88-117 of HBx were responsible for the binding to Hsp60. Confocal laser microscopy demonstrated that HBx and Hsp60 colocalized in mitochondria. Furthermore, terminal deoxynucleotidyl transferase-mediated dUTP end labeling (TUNEL) revealed that the introduction of Hsp60 into cells facilitated HBx-induced apoptosis. These findings suggest the importance of the molecular chaperon protein Hsp60 to the function of HBV viral proteins.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Kanai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kawakami
authors.forename: Keisuke
authors.initials: K
authors.lastname: Tateishi
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ijichi
authors.forename: Takao
authors.initials: T
authors.lastname: Kawabe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Takao
authors.initials: T
authors.lastname: Kawakami
authors.forename: Toshihide
authors.initials: T
authors.lastname: Nishimura
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Shirakata
authors.forename: Katsuro
authors.initials: K
authors.lastname: Koike
authors.forename: Masao
authors.initials: M
authors.lastname: Omata
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D002846:Chromatography, Affinity; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D013058:Mass Spectrometry; D008928:Mitochondria / Q000378:metabolism; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020539:Sequence Analysis, Protein / Q000379:methods; D017384:Sequence Deletion; D015534:Trans-Activators / Q000378:metabolism* / Q000502:physiology; D014162:Transfection; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D018834:Chaperonin 60; D011994:Recombinant Proteins; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein