Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P42574 (
caspase-3
)
45,978
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Mutations within the
Presenilin-2
(
PS-2
) gene are associated with early onset familial Alzheimer's disease. The gene encodes a polytopic transmembrane protein that undergoes endoproteolytic processing resulting in the generation of N-terminal and C-terminal fragments (CTFs).
PS-2
is also cleaved by proteases of the caspase family during apoptotic cell death. CTFs of
PS-2
were shown to inhibit apoptosis, suggesting an important role in the regulation of programmed cell death. Recently, we found that the CTF of
PS-2
is phosphorylated in vivo. We mapped the in vivo phosphorylation sites of
PS-2
to serine residues 327 and 330, which are localized immediately adjacent to the cleavage sites of caspases after aspartate residues 326 and 329. Phosphorylation of
PS-2
inhibits its cleavage by
caspase-3
. This effect can be mimicked by substitutions of serines 327 and 330 by aspartate or glutamate. In addition, the uncleavable form of
PS-2
CTF was found to enhance its antiapoptotic properties, leading to a slower progression of apoptosis. These results demonstrate that
PS-2
cleavage as well as its function in apoptosis can be regulated by protein phosphorylation. Alterations in the phosphorylation of
PS-2
may therefore promote the pathogenesis of AD by affecting the susceptibility of neurons to apoptotic stimuli.
...
PMID:Phosphorylation of presenilin-2 regulates its cleavage by caspases and retards progression of apoptosis. 999 34
A missense mutation (N1411) in
Presenilin-2
(
PS-2
) gene is associated with early-onset familial Alzheimer's disease. In this study, SK-N-SH human neuroblastoma cells were transfected with wild-type and mutant
PS-2
gene to examine presenilin-2 effects on apoptosis. Serum deprivation resulted in enhanced apoptosis in mutant
PS-2
comparing with wild-type
PS-2
. Similarly, mutant
PS-2
induced lactate dehydrogenase release to greater extent than wild-type
PS-2
. Time course experiment demonstrated that the increase in
caspase-3
-like activity was more pronounced and accelerated in mutant
PS-2
, compared to wild-type
PS-2
. While a significant decrease in bcl-2, an anti-apoptotic molecule, occurred in the cells overexpressing mutant
PS-2
, no significant change was observed in bax, a pro-apoptotic molecule, as compared with the cells overexpressing wild-type
PS-2
. Our study demonstrated that mutant
PS-2
induces apoptosis accompanied by increased
caspase-3
-like activity and decreased bcl-2 expression in neuronal cells after serum-deprivation.
...
PMID:N141I mutant presenilin-2 gene enhances neuronal cell death and decreases bcl-2 expression. 1217 18
