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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
Author(s) -
Wernersson Jonny,
Johansson Irja,
Larsson Ulrika,
MinthWorby Carolyn,
Påhlman Sven,
Andersson Göran
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70051887.x
Subject(s) - sh sy5y , transcription factor , trk receptor , tropomyosin receptor kinase a , microbiology and biotechnology , nerve growth factor , biology , response element , transcription (linguistics) , serum response factor , creb , neuroblastoma , chemistry , endocrinology , medicine , gene expression , receptor , promoter , gene , cell culture , biochemistry , genetics , linguistics , philosophy
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.