ACTIVATED TRANSCRIPTION OF THE HUMAN NEUROPEPTIDE-Y GENE IN DIFFERENTIATING SH-SY5Y NEUROBLASTOMA-CELLS IS DEPENDENT ON TRANSCRIPTION FACTORS AP-1, AP-2-ALPHA, AND NGFI

Activated transcription of the human neuropeptide Y gene (NPY) was inv estigated in SH-SY5Y neuroblastoma cells at the onset of sympathetic n euronal differentiation induced by 12-O-tetradecanoylphorbol 13-acetat e (TPA) and serum or by nerve growth factor (NGF). As determined by tr ansient expression, two NGF response elements (REs) were required for transcription induced by NGF in SH-SY5Y cells with stable expression o f an exogenous NGF receptor TRK-A gene (SH-SY5Y/trk). TPA treatment in the presence of serum induced NPY transcription in both wild-type SH- SY5Y (SH-SY5Y/wt) and SH-SY5Y/trk cells. A TPA RE (TRE), overlapping t he proximal NGF RE, was identified by expression of the v-Jun oncoprot ein that enhanced NPY transcription. Suppression of TPA-induced NPY tr anscription was obtained by expression of a dominant negative Jun prot ein, selective protein kinase C inhibition, or introduction of a mutat ed TRE, whereas NGF-induced NPY transcription was inhibited to a lesse r degree. The transcription factor AP-2 alpha was shown to bind cooper atively to the NPY promoter with either AP-1 or NGFI-A to the shared T RE and NGF RE and to the distal NGF RE, respectively. These results sh ow that transcription factors AP-1, AP-2 alpha, and NGFI-A are involve d in activated NPY transcription during the onset of neuronal differen tiation.