Overexpression of c-Fos is sufficient to stimulate tyrosine hydroxylase (TH) gene transcription in rat pheochromocytoma PC18 cells.

Abstract:

:The AP1 site within the tyrosine hydroxylase gene proximal promoter is essential for the response of the gene to numerous stimuli. Stimulation of this gene is often associated with induction of the AP1 transcription factor, c-Fos. However, many stimuli activate or induce multiple transcription factors that interact with this AP1 site or other sites within the gene's proximal promoter. Hence, it remains unclear whether c-Fos induction by itself is sufficient to stimulate the tyrosine hydroxylase gene. In this study we produce rat pheochromocytoma PC18 cells that overexpress c-Fos under control of the tet-inducible system. We demonstrate that induction of c-Fos leads to dramatic stimulation of tyrosine hydroxylase gene transcription rate measured using nuclear run-on assays. This stimulation is closely associated quantitatively with the induction of c-Fos and does not apparently require phosphorylation of c-Fos. The response is partially dependent on the AP1 site within the tyrosine hydroxylase proximal promoter. However, the response of the proximal promoter to c-Fos induction is relatively small compared with that of the endogenous gene. Consequently, our results suggest that c-Fos exerts its influence on the tyrosine hydroxylase gene via multiple mechanisms that are dependent and independent of the proximal promoter AP1 site.

journal_name

J Neurochem

authors

Sun B,Tank AW

doi

10.1046/j.0022-3042.2001.00692.x

keywords:

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

295-306

issue

2

eissn

0022-3042

issn

1471-4159

journal_volume

80

pub_type

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