%0 Journal Article
%T ¦Â-Catenin is a pH sensor with decreased stability at higher intracellular pH
%A Barber
%A Bree K. Grillo-Hill
%A Bui
%A Chire
%A Diane L.
%A Diane L. Barber
%A Esquivel
%A Ismahan
%A Ismahan Chire
%A Jobelle
%A Jobelle Peralta
%A Katharine A.
%A Katharine A. White
%A Mario
%A Mario Esquivel
%A Peralta
%A Vivian N.
%A Vivian N. Bui
%A White
%J JCB | The Journal of Cell Biology
%D 2018
%R 10.1083/jcb.201712041
%X ¦Â-Catenin functions as an adherens junction protein for cell¨Ccell adhesion and as a signaling protein. ¦Â-catenin function is dependent on its stability, which is regulated by protein¨Cprotein interactions that stabilize ¦Â-catenin or target it for proteasome-mediated degradation. In this study, we show that ¦Â-catenin stability is regulated by intracellular pH (pHi) dynamics, with decreased stability at higher pHi in both mammalian cells and Drosophila melanogaster. ¦Â-Catenin degradation requires phosphorylation of N-terminal residues for recognition by the E3 ligase ¦Â-TrCP. While ¦Â-catenin phosphorylation was pH independent, higher pHi induced increased ¦Â-TrCP binding and decreased ¦Â-catenin stability. An evolutionarily conserved histidine in ¦Â-catenin (found in the ¦Â-TrCP DSGIHS destruction motif) is required for pH-dependent binding to ¦Â-TrCP. Expressing a cancer-associated H36R¨C¦Â-catenin mutant in the Drosophila eye was sufficient to induce Wnt signaling and produced pronounced tumors not seen with other oncogenic ¦Â-catenin alleles. We identify pHi dynamics as a previously unrecognized regulator of ¦Â-catenin stability, functioning in coincidence with phosphorylation.
%U http://jcb.rupress.org/content/217/11/3965