Accumulation of ␤-catenin and subsequent stimulation of ␤-catenin-T cell-factor (Tcf)/lymphoid-enhancerfactor (Lef) transcriptional activity causes dedifferentiation of articular chondrocytes, which is characterized by decreased type II collagen expression and initiation of type I collagen expression. This study examined the mechanisms of ␣-catenin degradation, the role of ␣-catenin in ␤-catenin signaling, and the physiological significance of ␣-catenin regulation of ␤-catenin signaling in

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... ular chondrocytes. We found that both ␣and ␤-catenin accumulated during dedifferentiation of chondrocytes by escaping from proteasomal degradation. ␤-Catenin degradation was ubiquitination-dependent, whereas ␣-catenin was proteasomally degraded in a ubiquitination-independent fashion. The accumulated ␣and ␤-catenin existed as complexes in the cytosol and nucleus. The complex formation between ␣and ␤-catenin blocked proteasomal degradation of ␣-catenin and also inhibited ␤-catenin-Tcf/Lef transcriptional activity and the suppression of type II collagen expression associated with ectopic expression of ␤-catenin, the inhibition of proteasome, or Wnt signaling. Collectively, our results indicate that ubiquitin-independent degradation of ␣-catenin regulates ␤-catenin signaling and maintenance of the differentiated phenotype of articular chondrocytes.