Oncogenic β-catenin mutations evade pH-regulated degradation

Abstract

β-catenin has roles in cell-cell adhesion and Wnt signaling. We recently showed that β-catenin protein abundance is decreased at higher intracellular pH (pHi), mediated by pH-sensitive interaction with the beta-transducin repeat containing E3 ubiquitin protein ligase (β-TrCP). Increased pHi facilitates β-TrCP binding and degradation of β-catenin. β-catenin mutations that abrogate the pH-sensitive interaction induce significant tumors not seen with other β-catenin stabilizing mutants.

Keywords

• β-catenin
• intracellular ph
• wnt signaling
• ubiquitination
• proteasome
• β-trcp
• tumorigenesis