Up-regulation of [beta]-catenin by a viral oncogene correlates with inhibition of the seven in absentia homolog 1 in B lymphoma cells

The protein levels of [beta]-catenin are tightly regulated by the ubiquitin/proteasome system. We provide evidence that two distinct ubiquitin-dependent degradation pathways for [beta]-catenin are active in the same Burkitt's lymphoma cells: Along with the classical glycogen-synthase kinase 3[beta]-dependent destruction machinery, degradation of [beta]-catenin through seven in absentia homolog 1 (Siah-1) ubiquitin ligase is functional in these cells. We show that inhibition of endogenous Siah-1 stabilizes and activates [beta]-catenin in B cells. The principal Epstein-Barr virus oncoprotein, latent membrane protein 1, is involved in [beta]-catenin up-regulation, and expression of latent membrane protein 1 in B lymphoma cells is associated with decreased Siah-1 RNA and protein levels. Thus, we demonstrate the significance of the endogenous Siah-1-dependent ubiquitin/proteasome pathway for [beta]-catenin degradation in malignant human cells and its regulation by a viral oncogene. B lymphoma | ubiquitin/proteasomal degradation | Epstein-Barr virus | latent membrane protein 1