Accumulation of cytoplasmic beta-catenin and nuclear glycogen synthase kinase 3beta in Epstein-Barr virus-infected cells

• Published in: Journal of virology Vol. 78; no. 21; pp. 11648 - 11655
• Main Authors: Everly, Jr, David N, Kusano, Shuichi, Raab-Traub, Nancy
• Format: Journal Article
• Language: English
• Published: United States 01.11.2004
• Subjects: beta Catenin; Cell Line; Cytoplasm - metabolism; Cytoskeletal Proteins - metabolism; Glycogen Synthase Kinase 3 - metabolism; Glycogen Synthase Kinase 3 beta; Herpesvirus 4, Human - physiology; Humans; Lymphocytes - metabolism; Phosphorylation; Trans-Activators - metabolism
• ISSN: 0022-538X

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with cancers in immunocompromised populations. EBV establishes a latent infection and immortalizes and transforms B lymphocytes. Several latent proteins have profound effects on cellular growth, including activation of NF-kappaB, phosphatidylinositol 3'-OH kinase (PI3K) signaling, and notch signaling. Activation of PI3K can affect the activity of beta-catenin, the target of the wnt signaling pathway. Deregulation of beta-catenin is associated with a number of malignancies. To determine if beta-catenin is regulated by EBV infection, EBV-infected cells were examined for beta-catenin levels and localization. beta-Catenin was increased in EBV-positive tumor cell lines compared to EBV-negative lines, in EBV-infected Burkitt's lymphoma cell lines, and in EBV-transformed lymphoblastoid cell lines (LCL). In contrast to wnt signaling, EBV consistently induced the accumulation of beta-catenin in the cytoplasm but not the nucleus. The beta-catenin regulating kinase, glycogen synthase kinase 3beta (GSK3beta), was shown to be phosphorylated and inactivated in EBV-infected lymphocytes. Inactivated GSK3beta was localized to the nucleus of EBV-infected LCL. Neither the cytoplasmic accumulation of beta-catenin nor the nuclear inactivation of GSK3beta was affected by the inhibition of PI3K signaling. These data indicate that latent infection with EBV has unique effects on beta-catenin signaling that are distinct from activation of wnt and independent of its effects on PI3K.