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

被引:60
作者
Tesco, G
Kim, TW
Diehlmann, A
Beyreuther, K
Tanzi, RE
机构
[1] Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA
[2] Harvard Med Sch, Charlestown, MA 02129 USA
[3] Zentrum Mol Biol, INF 282, D-69120 Heidelberg, Germany
关键词
D O I
10.1074/jbc.273.51.33909
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页码:33909 / 33914
页数:6
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