Premium
Apoptotic action of E2F1 requires glycogen synthase kinase 3‐β activity in PC12 cells
Author(s) -
Espada Lilia,
Udapudi Basavaraj,
Podlesniy Petar,
Fabregat Isabel,
Espinet Carme,
Tauler Albert
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04686.x
Subject(s) - e2f1 , apoptosis , gsk 3 , biology , microbiology and biotechnology , cancer research , signal transduction , cell cycle , biochemistry
Both E2F1 and GSK3β have been described as essential targets in neuronal apoptosis. Previous studies have demonstrated that GSK3β binds to E2F1 in vivo . We wanted to investigate whether these proteins could share a common apoptotic signal pathway in neuronal cells. With this intention, we developed a PC12 ER‐E2F1 stable cell line in which E2F1 activity was dependent on the presence of 4‐hydroxitamoxifen. E2F1 activation produced apoptosis in naive and post‐mitotic cells; serum and nerve growth factor respectively protected them from E2F1 apoptotic stimuli. The presence of specific GSK3β inhibitors SB216763 and LiCl completely protected cells from apoptosis induced by E2F1 activation. In addition, knocked down GSK3β experiments by small interference RNAs have demonstrated that a reduction of GSK3β protein levels can lower the apoptotic effect of E2F1. Finally, we demonstrated that the apoptotic effect of E2F1 is not due to the regulation of GSK3β activity, and that the inhibitory effect of GSK3β inhibitor SB216763 on E2F1 induced apoptosis could be due to an alteration in the E2F1‐regulated transcription gene pattern. In summary, we have demonstrated that the apoptotic action of E2F1 requires GSK3β activity.