SERINE PHOSPHORYLATION-REGULATED UBIQUITINATION AND DEGRADATION OF BETA-CATENIN

Several lines of evidence suggest that accumulation of cytoplasmic bet a-catenin transduces an oncogenic signal We show that beta-catenin is ubiquitinated and degraded by the proteosome and that beta-catenin sta bility is regulated by a diacylglycerol-independent protein kinase C-l ike kinase activity, which is required for beta-catenin ubiquitination . We also define a sis-amino acid sequence found in both beta-catenin and the NF-kappa B regulatory protein I kappa B alpha, which, upon pho sphorylation, targets both proteins for ubiquitination. Mutation of a single serine within the ubiquitination targeting sequence prevents ub iquitination of beta-catenin. Mutations within the ubiquitination targ eting sequence of beta-catenin may be oncogenic.