Abstract
Accumulation of beta-catenin and subsequent stimulation of beta-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 alpha-catenin degradation, the role of alpha-catenin in beta-catenin signaling, and the physiological significance of alpha-catenin regulation of beta-catenin signaling in articular chondrocytes. We found that both alpha- and beta-catenin accumulated during dedifferentiation of chondrocytes by escaping from proteasomal degradation. Beta-catenin degradation was ubiquitination-dependent, whereas alpha-catenin was proteasomally degraded in a ubiquitination-independent fashion. The accumulated alpha- and beta-catenin existed as complexes in the cytosol and nucleus. The complex formation between alpha- and beta-catenin blocked proteasomal degradation of alpha-catenin and also inhibited beta-catenin-Tcf/Lef transcriptional activity and the suppression of type II collagen expression associated with ectopic expression of beta-catenin, the inhibition of proteasome, or Wnt signaling. Collectively, our results indicate that ubiquitin-independent degradation of alpha-catenin regulates beta-catenin signaling and maintenance of the differentiated phenotype of articular chondrocytes.
Highlights
-Catenin interacts with cadherin to participate in cell-cell adhesion and regulates gene expression by acting as a transcriptional co-activator [1, 2]
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
Ubiquitin-independent Proteasomal Degradation of ␣-Catenin in Articular Chondrocytes—Based on previous reports that -catenin levels were regulated by proteasomal degradation [3], we first examined whether the proteasomal degradation pathway regulates ␣-catenin protein level in primary cultured articular chondrocytes
Summary
T cell-factor; Lef, lymphoid-enhancer-factor; ALLnL, N-acetyl-leucyl-leucyl-norleucinal; ALLM, N-acetylleucyl-leucyl-methioninal; siRNA, small interference RNA; RT, reverse transcription; GFP, green fluorescent protein; ERK, extracellular signal-regulated kinase; Z, benzyloxycarbonyl; fmk, fluoromethyl ketone; CBZ, carbamazepine; Suc, succinic acid; MCA, 3-methylcholanthrene. ␣-Catenin Degradation in -Catenin Signaling investigated the mechanisms of ␣-catenin degradation, the role of ␣-catenin in -catenin signaling, and the physiological significance of ␣-catenin regulation of -catenin signaling in articular chondrocytes
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call