Tesco G, Kim T W, Diehlmann A, Beyreuther K, Tanzi R E
Genetics and Aging Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
J Biol Chem. 1998 Dec 18;273(51):33909-14. doi: 10.1074/jbc.273.51.33909.
beta-Catenin has previously been shown to interact with presenilin 1 (PS1) in transfected cells. Here we report that beta-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, beta-catenin and PS1-CTF undergo a caspase-mediated cleavage. After 12 h of STS treatment, the beta-catenin.PS1-CTF interaction is abrogated. While PS1-CTF immunoprecipitated with all caspase-cleaved species of beta-catenin, beta-catenin holoprotein did not co-immunoprecipitate with the "alternative" caspase-derived PS1-CTF (PS1-aCTF). Thus, the abrogation of the beta-catenin.PS1-CTF complex was due to caspase cleavage of PS1-CTF. beta-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 beta-catenin was abolished. Thus, while the PS1-NTF.CTF complex is preserved after caspase cleavage, it may no longer be fully functional.
此前已表明，β-连环蛋白在转染细胞中可与早老素1（PS1）相互作用。在此我们报告，在H4人神经胶质瘤细胞中，β-连环蛋白与早老素1的内源性C末端片段（PS1-CTF）发生共免疫沉淀，但不与早老素2的内源性C末端片段（PS2-CTF）发生共免疫沉淀。在星形孢菌素（STS）诱导的细胞死亡过程中，β-连环蛋白和PS1-CTF会发生半胱天冬酶介导的切割。STS处理12小时后，β-连环蛋白与PS1-CTF的相互作用被消除。虽然PS1-CTF与所有经半胱天冬酶切割的β-连环蛋白物种发生免疫沉淀，但β-连环蛋白全蛋白不与“替代性”半胱天冬酶衍生的PS1-CTF（PS1-aCTF）发生共免疫沉淀。因此，β-连环蛋白与PS1-CTF复合物的消除是由于PS1-CTF的半胱天冬酶切割。β-连环蛋白与PS1-NTF发生共免疫沉淀，但仅当PS1-NTF与PS1-CTF相关联时才会发生。尽管半胱天冬酶切割未改变PS1-NTF与CTF复合物的稳定性，但其结合β-连环蛋白的能力被消除。因此，虽然半胱天冬酶切割后PS1-NTF与CTF复合物得以保留，但其可能不再具有完全功能。
