Activated Transcription of the Human Neuropeptide Y Gene in Differentiating SH-SY5Y Neuroblastoma Cells Is Dependent on Transcription Factors AP-1, AP-2Α, and NGFI

Activated transcription of the human neuropeptide Y gene ( NPY ) was investigated in SH-SY5Y neuroblastoma cells at the onset of sympathetic neuronal differentiation induced by 12- O -tetradecanoylphorbol 13-acetate (TPA) and serum or by nerve growth factor (NGF). As determined by transient expression, two NGF response elements (REs) were required for transcription induced by NGF in SH-SY5Y cells with stable expression of 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 the proximal NGF RE, was identified by expression of the v-Jun oncoprotein that enhanced NPY transcription. Suppression of TPA-induced NPY transcription was obtained by expression of a dominant negative Jun protein, selective protein kinase C inhibition, or introduction of a mutated TRE, whereas NGF-induced NPY transcription was inhibited to a lesser degree. The transcription factor AP-2Α was shown to bind cooperatively to the NPY promoter with either AP-1 or NGFI-A to the shared TRE and NGF RE and to the distal NGF RE, respectively. These results show that transcription factors AP-1, AP-2Α, and NGFI-A are involved in activated NPY transcription during the onset of neuronal differentiation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65864/1/j.1471-4159.1998.70051887.x.pd