title: Epstein-Barr virus latent membrane protein 1 induces CD69 expression through activation of nuclear factor-κB.
abstract: Latent membrane protein‑1 (LMP-1) of Epstein‑Barr virus (EBV) promotes tumorigenesis. Here, we report that LMP-1 activates the immunoregulatory molecule CD69 gene transcription through a nuclear factor-κB (NF-κB)‑dependent pathway. CD69 expression was upregulated in LMP-1‑expressing EBV-immortalized human B-cell lines and an EBV-positive Burkitt's lymphoma cell line. LMP-1 expression increased CD69 expression at the transcriptional level. CD69 promoter was regulated by LMP-1 activation of NF-κB via the carboxy-terminal activation region 1 and 2. Promoter deletion analysis indicated that two NF-κB binding sites are necessary for activation of the CD69 promoter. Electrophoretic mobility shift analysis demonstrated that LMP-1 activates both NF-κB binding sites in the CD69 promoter. This is the first report of the regulation of CD69 expression by LMP-1, and this novel finding may, thus, represent an important link between the EBV oncoprotein LMP-1 and its critical role in the development of EBV-associated diseases.
authors.affiliation: Transdisciplinary Research Organization for Subtropics and Island Studies, Nishihara, Okinawa 903-0213, Japan. chiezo@lab.u-ryukyu.ac.jp
authors.forename: Chie
authors.initials: C
authors.lastname: Ishikawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
mesh_terms: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D001665:Binding Sites / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type; D016328:NF-kappa B / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D015398:Signal Transduction; D015533:Transcriptional Activation; D015854:Up-Regulation; D014763:Viral Matrix Proteins / Q000235:genetics / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D037181:Lectins, C-Type; D016328:NF-kappa B; D014763:Viral Matrix Proteins; D000099192:CD69 Antigens; C037662:EBV-associated membrane antigen, Epstein-Barr virus