β-Catenin-RAS interaction serves as a molecular switch for RAS degradation via GSK3β

ABSTRACT: RAS proteins play critical roles in various cellular processes, including growth and transformation. RAS proteins are subjected to protein stability regulation via the Wnt/β-catenin pathway, and glycogen synthase kinase 3 beta (GSK3β) is a key player for the phosphorylation-dependent RAS degradation through proteasomes. GSK3β-mediated RAS degradation does not occur in cells that express a nondegradable mutant (MT)-β-catenin. Here, we show that β-catenin directly interacts with RAS at the α-interface region that contains the GSK3β phosphorylation sites, threonine-144 and threonine-148 residues. Exposure of these sites by prior β-catenin degradation is required for RAS degradation. The introduction of a peptide that blocks the β-catenin-RAS interaction by binding to β-catenin rescues the GSK

SUBMITTER: Dr. Sang-Kyu Lee 

PROVIDER: S-SCDT-EMBOR-2018-46060-T | biostudies-other |

REPOSITORIES: biostudies-other