Dishevelled-KSRP complex regulates Wnt signaling through post-transcriptional stabilization of beta-catenin mRNA.

ABSTRACT

Canonical Wnt/beta-catenin signaling is crucial during embryonic development. Upon Wnt stimulation, Dishevelled proteins relay the signal from upstream Frizzled receptors to downstream effectors. By using affinity purification followed by ion-trap mass spectrometry we identified K-homology splicing regulator protein (KSRP) as a novel Dishevelled-interacting protein. We show that KSRP negatively regulates Wnt/beta-catenin signaling at the level of post-transcriptional CTNNB1 (beta-catenin) mRNA stability. Thus, Dishevelled-KSRP complex operates in Wnt regulation of beta-catenin, functioning post-transcriptionally upon CTNNB1 mRNA stability.