Oncogenic β-catenin mutations evade pH-regulated degradation

Bree K Grillo-Hill; Katharine A White

doi:10.1080/23723556.2018.1554470

Oncogenic β-catenin mutations evade pH-regulated degradation

Mol Cell Oncol. 2019 Jan 2;6(1):1554470. doi: 10.1080/23723556.2018.1554470. eCollection 2019.

Authors

Bree K Grillo-Hill¹, Katharine A White^{2

3}

Affiliations

¹ Department of Biological Sciences, San Jose State University, San Jose, CA, USA.
² Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, CA, USA.
³ Department of Chemistry and Biochemistry, Harper Cancer Research Institute, University of Notre Dame, South Bend, IN, USA.

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: Wnt signaling; intracellular pH; proteasome; tumorigenesis; ubiquitination; β-TrCP; β-catenin.