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 prot eolytically cleaved during anoikis and staurosporine-induced apoptosis, Cle avage of beta-catenin was found to be caspase-dependent. Five cleavage prod ucts of beta-catenin were identified in vivo and after in vivo cleavage by caspase-3. Amino acid sequencing and mass spectrometry analysis indicated t wo caspase-3 cleavage sites at the C terminus and three further sites at th e N terminus, whereas the central Armadillo repeat region remained unaffect ed. 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 resembli ng the observed proteolytic fragments show a strongly reduced transcription activation potential when analyzed in gene reporter assays. We therefore c onclude that an important role of the beta-catenin cleavage during apoptosi s is the removal of its transcription activation domains to prevent its tra nscription activation potential.