title: Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) forms complexes with a cellular anti-apoptosis protein Bcl-2 or its EBV counterpart BHRF1 through HS1-associated protein X-1.
abstract: Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) plays a critical role in EBV-induced transformation. An earlier report (Y. Kawaguchi et al., J. Virol. 74: 10104-10111, 2000) showed that EBNA-LP interacts with a cellular protein HS1-associated protein X-1 (HAX-1). The predicted amino acid sequence of HAX-1 exhibits similarity to that of another cellular protein Nip3 which has been shown to interact with cellular and viral anti-apoptotic proteins such as Bcl-2 and BHRF1, an EBV homolog of Bcl-2. Here we investigated whether HAX-1, like Nip3, interacts with Bcl-2 proteins and report the following. (i) A purified chimeric protein consisting of gluthathione S-transferase (GST) fused to BHRF1 (GST-BHRF1) or Bcl-2 (GST-Bcl-2) specifically pulled down HAX-1 transiently expressed in COS-7 cells. (ii) GST-BHRF1 or GST-Bcl-2 was not able to pull down EBNA-LP transiently expressed in COS-7 cells, whereas each of the GST fusion proteins formed complexes with EBNA-LP in the presence of RAX-1. These results indicated that EBNA-LP interacts with the viral and cellular Bcl-2 proteins through HAX-1, suggesting that EBNA-LP possesses a potential function in the regulation of apoptosis in EBV-infected cells.
authors.affiliation: Department of Cell Regulation, Medical Research Institute, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8510, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Matsuda
authors.forename: Kaori
authors.initials: K
authors.lastname: Nakajima
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Yamanashi
authors.forename: Kanji
authors.initials: K
authors.lastname: Hirai
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D019556:COS Cells; D002522:Chlorocebus aethiops; D019309:Epstein-Barr Virus Nuclear Antigens / Q000276:immunology / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics; D004854:Herpesvirus 4, Human / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics; D016415:Sequence Alignment; D014162:Transfection; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C083278:BHRF1 protein, Human herpesvirus 4; C402640:EBNA-LP protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; C104759:HAX1 protein, human; D011506:Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D014764:Viral Proteins