Small molecule-based disruption of the Axin/β-catenin protein complex regulates mesenchymal stem cell differentiation.

ABSTRACT: The Wnt/β-catenin pathway plays important roles in the differentiation of multiple cell types, including mesenchymal stem cells. Using a cell-based chemical screening assay with a synthetic chemical library of 270 000 compounds, we identified the compound SKL2001 as a novel agonist of the Wnt/β-catenin pathway and uncovered its molecular mechanism of action. SKL2001 upregulated β-catenin responsive transcription by increasing the intracellular β-catenin protein level and inhibited the phosphorylation of β-catenin at residues Ser33/37/Thr41 and Ser45, which would mark it for proteasomal degradation, without affecting CK1 and GSK-3β enzyme activities. Biochemical analysis revealed that SKL2001 disrupted the Axin/β-catenin interaction, which is a critical step for CK1- and GSK-3β-mediated pho

SUBMITTER: Gwak J 

PROVIDER: S-EPMC3351914 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature