Apoptosis-induced cleavage of beta-catenin by caspase-3 results in proteolytic fragments with reduced transactivation potential

Item Type:	Article
Title:	Apoptosis-induced cleavage of beta-catenin by caspase-3 results in proteolytic fragments with reduced transactivation potential
Creators Name:	Steinhusen, U. and Badock, V. and Bauer, A. and Behrens, J. and Wittmann-Liebold, B. and Doerken, B. and Bommert, K.
Abstract:	{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.
Keywords:	Apoptosis, Beta Catenin, Cadherins, Caspase 3, Caspases, Cell Adhesion, Cell Line, Cytoskeletal Proteins, Flow Cytometry, Oligopeptides, Peptide Fragments, Protein Binding, Recombinant Proteins, Reporter Genes, Trans-Activation (Genetics), Trans-Activators
Source:	Journal of Biological Chemistry
ISSN:	0021-9258
Publisher:	American Society for Biochemistry and Molecular Biology
Volume:	275
Number:	21
Page Range:	16345-16353
Date:	1 January 2000
Official Publication:	https://doi.org/10.1074/jbc.M001458200
PubMed:	View item in PubMed

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