Up-regulation of beta-catenin by a viral oncogene correlates with inhibition of the seven in absentia homolog 1 in B lymphoma cells.
Proceedings of the National Academy of Sciences of the United States of America 2005 Dec 20; 102(51):18431-6
Jang K KL, Shackelford J J, Seo S SY, Pagano J JS
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599-7295, USA.
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 3beta-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.