Background: In the ubiquitin-proteasome pathway, the ubiquitinated substrates either undergo degradation by the proteasome or stabilization through the action of the deubiquitinating enzyme. We have previously found that the deubiquitinating enzyme Fam is colocalized with AF-6, one of the effectors of the Ras small GTPase, at cell-cell contact sites in epithelial cells and interacts with AF-6 in vivo and in vitro. Fam has deubiquitinating activity in vitro and prevents the ubiquitination of AF-6 in intact cells. The degradation of β-catenin, which accumulates at the cell-cell contact sites as a cadherin/catenin complex, is thought to be regulated by the ubiquitin-proteasome pathway. These observations prompted us to examine the possible Fam regulation of the stabilization of β-catenin. Results: We found that Fam interacted with β-catenin both in vivo and in vitro. The Fam- binding site of β-catenin mapped to the region close to the APC or Axin- binding site of β-catenin. Overexpression of Fam in mouse L cells resulted in an elevation of β-catenin levels and in an elongation of the half-life of β-catenin. In these L cells, Fam was colocalized with β-catenin at the dot- like structures in the cytoplasm. Conclusion: These results indicate that Fam interacts with and stabilizes β-catenin in vivo, presumably through the deubiquitination of β-catenin.
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