Activated transcription of the human neuropeptide Y gene in differentiating SH-SY5Y neuroblastoma cells is dependent on transcription factors AP-1, AP-2alpha, 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-2alpha 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-2alpha, and NGFI-A are involved in activated NPY transcription during the onset of neuronal differentiation.
Wernersson
J
J
Department of Pathology, Uppsala University, University Hospital, Sweden.
Johansson
I
I
Larsson
U
U
Minth-Worby
C
C
Påhlman
S
S
Andersson
G
G
D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D051766:Early Growth Response Protein 1; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D009154:Mutation / Q000502:physiology; D009414:Nerve Growth Factors / Q000494:pharmacology; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors / Q000235:genetics*; D016759:Oncogene Protein p65(gag-jun) / Q000378:metabolism / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D009414:Nerve Growth Factors; D009478:Neuropeptide Y; D016759:Oncogene Protein p65(gag-jun); D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate