Dual functions of AP-1 in neuronal cell death and differentiation

Abstract

Dual functions of AP-1 (c-Jun is a major component of AP-1 dimer) in cell death were discovered by the current study in a single neuroblastoma cell line (SH-Sy5y cells) in response to a single stimulus (NO, nitric oxide): basal c-Jun/AP-1 activity (in the absence of NO stimulation) is important for neuroprotection from NO-caused apoptosis through regulation of the expression of sgII (secretogranin II) and NCAM140 (neural cell adhesion molecule 140); whereas at toxic concentrations of NO, c-Jun is phosphorylated exclusively on Ser-63 in JNK-dependent manner, which enhances c-Jun/AP-1 transcriptional activity, counteracts the protective function of basal AP-1, and eventually leads to apoptosis in SH-Sy5y cells. Besides, AP-1 is also crucial for NGF-induced neuronal differentiation in SH-Sy5y cells, partly through regulating the expression of its target gene sgII and NCAM140.