Abrogation of the presenilin 1/β-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase activation

Abstract

β-Catenin has previously been shown to interact with presenilin 1 (PSI) in transfected cells. Here we report that β-catenin co-immunoprecipitates with the endogenous C-terminal fragment of presenilin 1 (PS1-CTF) but not with the endogenous CTF of presenilin 2 (PS2-CTF) in H4 human neuroglioma cells. During staurosporine (STS)-induced cell death, β-catenin and PS1-CTF undergo a caspase-mediated cleavage. After 12 h of STS treatment, the β- catenin. PS1-CTF interaction is abrogated. While PS1-CTF immunoprecipitated with all caspase-cleaved species of β-catenin, β-catenin holoprotein did not co-immunoprecipitate with the 'alternative' caspase-derived PS1-CTF (PSI- aCTF). Thus, the abrogation of the β-catenin. PS1-CTF complex was due to caspase cleavage of PS1-CTF. β-Catenin co-immunoprecipitated with PS1-NTF, but only when PS1-NTF was associated with PS1-CTF. Even though PS1-NTF·CTF complex stability was not altered by caspase cleavage, its ability to bind β-catenin was abolished. Thus, while the PS1-NTF·CTF complex is preserved after caspase cleavage, it may no longer be fully functional.