Regulation of beta-catenin signaling and maintenance of chondrocyte differentiation by ubiquitin-independent proteasomal degradation of alpha-catenin

J Biol Chem. 2005 Apr 1;280(13):12758-65. doi: 10.1074/jbc.M413367200. Epub 2005 Jan 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cartilage, Articular / cytology*
  • Cell Differentiation
  • Cell Nucleus / metabolism
  • Chondrocytes / cytology*
  • Chondrocytes / metabolism
  • Collagen / metabolism
  • Cytoskeletal Proteins / metabolism*
  • Cytosol / metabolism
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation
  • Genetic Vectors
  • Immunoprecipitation
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Luciferases / metabolism
  • Microscopy, Fluorescence
  • Molecular Sequence Data
  • Proteasome Endopeptidase Complex / metabolism*
  • RNA, Small Interfering / metabolism
  • Rabbits
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction*
  • Subcellular Fractions / metabolism
  • Time Factors
  • Trans-Activators / metabolism*
  • Transcription, Genetic
  • Transfection
  • Ubiquitin / metabolism*
  • Wnt Proteins
  • alpha Catenin
  • beta Catenin

Substances

  • Cytoskeletal Proteins
  • DNA, Complementary
  • Intercellular Signaling Peptides and Proteins
  • RNA, Small Interfering
  • Trans-Activators
  • Ubiquitin
  • Wnt Proteins
  • alpha Catenin
  • beta Catenin
  • Collagen
  • Luciferases
  • Proteasome Endopeptidase Complex
  • ATP dependent 26S protease

Associated data

  • GENBANK/AB193105