Epstein-Barr virus activates beta-catenin in type III latently infected B lymphocyte lines: association with deubiquitinating enzymes.
beta-Catenin is a multifunctional protein, stabilization of which is a critical step in its functional activity. Stabilization can be conferred through several means, including mutations in beta-catenin, common in many carcinomas. In this article, we explore the effect of viral infection on the beta-catenin signaling pathway in B lymphocytes, including cell lines derived from lymphomas. Infection by the human tumor virus Epstein-Barr virus (EBV) generates several types of latency with different spectra of latent gene expression that are associated with different malignancies. In type III latency, exemplified by EBV lymphoproliferative diseases, the full range of these viral proteins is expressed, whereas in type I latency, only the EBNA1 protein is expressed and functional. We show that beta-catenin is rapidly degraded in type I B lymphocytic lines but it is stabilized in type III B cell lines, and that beta-catenin/T cell factor transcriptional activity is significantly higher in type III cells. Also we show the association of free cytoplasmic beta-catenin with deubiquitinating enzymes, which may play a role in beta-catenin stabilization. Activation of the beta-catenin/T cell factor pathway by EBV may contribute to the lymphoproliferation characteristic of type III latency.
Shackelford
Julia
J
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
Maier
Christopher
C
Pagano
Joseph S
JS
D001402:B-Lymphocytes / Q000821:virology*; D015820:Cadherins / Q000378:metabolism; D002460:Cell Line; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D015534:Trans-Activators / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D025801:Ubiquitin / Q000378:metabolism*; D017735:Virus Latency; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D015853:Cysteine Proteinase Inhibitors; D003598:Cytoskeletal Proteins; D007976:Leupeptins; D009097:Multienzyme Complexes; D015534:Trans-Activators; D025801:Ubiquitin; D051176:beta Catenin; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde