Inhibition of HOS Expression and Activities by Wnt Pathway

BetaTrCP and HOS are closely related F-box proteins, which play key roles in ubiquitination and degradation of beta-catenin and IkappaB through associating with those phosphorylated substrates and recruiting SCF E3 ubiquitin ligase. Here we report that activation of Wnt/beta-catenin signal transduction pathway elevates betaTrCP levels but inhibits expression of HOS in 293T cells. Similar disparity is likely to exist in human colorectal tumors. In the NIH3T3 cells, which express HOS, but not betaTrCP, Wnt/beta-catenin signaling leads to inhibition of HOS promoter activity and NF-kappaB-driven transcription as well as to stabilization of beta-catenin. These results indicate that expression and activities of HOS are negatively regulated by Wnt/beta-catenin pathway.