Abrogation of the presenilin 1/beta-catenin interaction and preservation of the heterodimeric presenilin 1 complex following caspase activation.
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.
Tesco
G
G
Genetics and Aging Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Kim
T W
TW
Diehlmann
A
A
Beyreuther
K
K
Tanzi
R E
RE
D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D019281:Dimerization; D005910:Glioma; D006801:Humans; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010446:Peptide Fragments / Q000302:isolation & purification / Q000378:metabolism; D053764:Presenilin-1; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; D011994:Recombinant Proteins; D015534:Trans-Activators; D051176:beta Catenin; D020169:Caspases; D019311:Staurosporine