1. Molecular Mechanisms of Neuronal Cell Death: Implications for Nuclear Factors Responding to cAMP and Phorbol Esters
- Author
-
Vyas, Sheela, Biguet, Nicole Faucon, Michel, Patrick P., Monaco, Lucia, Foulkes, Nicholas S., Evan, Gerard I., Sassone-Corsi, Paolo, and Agid, Yves
- Subjects
- *
IONOPHORES , *APOPTOSIS - Abstract
Chronic treatment with calcium ionophore A23187 in NGF-differentiated cells results in cell death that is time- and concentration-dependent. Additionally, PC12 cells codifferentiated with NGF and dBcAMP become dependent on these factors for survival and undergo apoptosis when both factors are withdrawn. We show that in both cases there is a prolonged induction of c-Fos which correlates with cell death. Its continual activation in PC12 cells overexpressing c-FosER results in caspase-3 cleavage and rapid cell death. Specific phosphorylation of CREB/CREMτ transactivators or their binding to CRE of c-fos was observed. Our results indicate that prolonged c-Fos induction activates p53. There is increased nuclear localization of p53, p21 and Bax levels are induced in NGF/dBcAMP-deprived c-FosER cells, and dominant negative p53 inhibits cell death induced either by serum deprivation or by c-Fos. Overall these data implicate AP-1 as a nuclear target of signal transduction pathways which plays a role in the activation of apoptosis. [Copyright &y& Elsevier]
- Published
- 2002
- Full Text
- View/download PDF