Apoptosis-induced cleavage of beta-catenin by caspase-3 results in proteolytic fragments with reduced transactivation potential.
Beta-catenin is a member of the Armadillo repeat protein family with a dual cellular function as a component of both the adherens junction complex and the Wnt/wingless signaling pathway. Here we show that beta-catenin is proteolytically cleaved during anoikis and staurosporine-induced apoptosis. Cleavage of beta-catenin was found to be caspase-dependent. Five cleavage products of beta-catenin were identified in vivo and after in vitro cleavage by caspase-3. Amino acid sequencing and mass spectrometry analysis indicated two caspase-3 cleavage sites at the C terminus and three further sites at the N terminus, whereas the central Armadillo repeat region remained unaffected. All beta-catenin cleavage products were still able to associate with E-cadherin and alpha-catenin and were found to be enriched in the cytoplasm. Functional analysis revealed that beta-catenin deletion constructs resembling the observed proteolytic fragments show a strongly reduced transcription activation potential when analyzed in gene reporter assays. We therefore conclude that an important role of the beta-catenin cleavage during apoptosis is the removal of its transcription activation domains to prevent its transcription activation potential.
Steinhusen
U
U
Max-Delbrück-Center for Molecular Medicine, Department of Medical Oncology and Tumorimmunology, Robert-Rössle-Strasse 10, D-3092, Berlin, Germany.
Badock
V
V
Bauer
A
A
Behrens
J
J
Wittman-Liebold
B
B
Dörken
B
B
Bommert
K
K
D017209:Apoptosis; D015820:Cadherins / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry; D011485:Protein Binding; D011994:Recombinant Proteins; D015534:Trans-Activators; D015533:Transcriptional Activation / Q000235:genetics*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D009842:Oligopeptides; D010446:Peptide Fragments; D011994:Recombinant Proteins; D015534:Trans-Activators; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D051176:beta Catenin; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases