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GMF overexpression causes apoptosis in neuroblastoma cells
Author(s) -
Zaheer Asgar,
Knight Scott,
Zaheer Ashna,
Ahrens Marcus,
Sahu Shailendra K.,
Yang Baoli
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.648.16
Subject(s) - apoptosis , microbiology and biotechnology , protein kinase b , signal transduction , biology , caspase 3 , chemistry , cancer research , programmed cell death , biochemistry
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. Overexpression of GMF in N18 cells is correlated with the increase in toxicity and loss of cell viability. A significant increase in GSK‐3beta activity occurred after infection with GMF‐V compared to the no infection (mock) and lacZ controls. Overexpression of GMF also increased caspase‐3 activity, an early marker of apoptosis. Depletion of GMF mRNA by introducing GMF‐specific siRNA completely blocked GSK‐3beta and caspase‐3 activation whereas control scrambled siRNA had no effect. A cell‐permeable specific inhibitor of GSK‐3beta and lithium completely prevented GMF‐dependent activation of caspase‐3. Our results demonstrate that GMF is involved in the signaling leading to the activation of GSK‐3beta, caspase‐3 and inactivation of Akt in neuroblastoma cells and strongly suggest the involvement of GMF in neuro degeneration. This is the first study to demonstrate that GMF overexpression causes apoptosis through activation of the GSK‐caspase‐mediated signaling mechanism.