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: EC:2.7.11.26 (
GSK
)
6,788
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
In the present study we report that a replication-defective adenovirus construct of
GMF
cDNA (
GMF
-V) induced overexpression of
GMF
protein in neuroblastoma (N18) cells caused cytotoxicity and loss of cell viability. A significant increase in activation of
GSK
-3beta occurred after infection with
GMF
-V when compared with mock and lacZ controls. Overexpression of
GMF
also increased caspase-3 activity, an early marker of apoptosis. Depletion of
GMF
gene by introducing
GMF
-specific siRNA (GsiRNA) completely blocked both activation of
GSK
-3beta and caspase-3 activation whereas a control scrambled siRNA (CsiRNA) had no effect. A cell-permeable peptide inhibitor of
GSK
-3beta, and lithium completely prevented
GMF
-dependent activation of caspase-3. These results demonstrate that
GSK
-3 mediates activation of the death domain caspase by
GMF
overexpression. We also show that the phosphorylation of
GSK
-3-dependent site of Tau was a consequence of
GMF
-overexpression in N18 cells. Taken together our results imply that
GMF
is involved in the signaling leading to the activation of
GSK
-3beta and caspase-3 in N18 cells and strongly suggest its involvement in neurodegeneration since
GSK
-3beta is known to hyperphosphorylate tau which is associated with the neurotoxicity of neurofibrillary tangles in Alzheimer's disease.
...
PMID:Glia maturation factor overexpression in neuroblastoma cells activates glycogen synthase kinase-3beta and caspase-3. 1805 98
