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Up‐regulation of tyrosine hydroxylase gene transcription by tetradecanoylphorbol acetate is mediated by the transcription factors Ets‐like protein‐1 (Elk‐1) and Egr‐1
Author(s) -
Stefano Luisa,
Sarraj Jude,
Rössler Oliver G.,
Vinson Charles,
Thiel Gerald
Publication year - 2006
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 - 10.1111/j.1471-4159.2006.03749.x
Subject(s) - tyrosine hydroxylase , transcription factor , microbiology and biotechnology , response element , tcf4 , sp1 transcription factor , biology , enhancer , e box , general transcription factor , tyrosine 3 monooxygenase , sp3 transcription factor , promoter , gene expression , chemistry , gene , biochemistry , enzyme
Tyrosine hydroxylase is the rate‐limiting enzyme in the biosynthesis of catecholamines. Expression of the tyrosine hydroxylase gene is regulated at the transcriptional level by extracellular signalling molecules, including epidermal growth factor (EGF), nerve growth factor (NGF) and glucocorticoids. We have analysed the stimulation of tyrosine hydroxylase gene transcription by the phorbol ester 12‐ O ‐tetradecanoylphorbol‐13‐acetate (TPA) in noradrenergic locus coeruleus‐like CATH.a cells and observed a striking enhancement of the transcriptional activation potential of the ternary complex factor Ets‐like protein‐1 (Elk‐1), a key transcriptional regulator of serum response element‐driven gene transcription. Likewise, TPA strongly up‐regulated the biosynthesis of the transcription factor Egr‐1 via distal serum response elements within the Egr‐1 5′‐flanking region. Subsequently, enhancement of the transcriptional activation potential of Egr‐1 was observed. Overexpression of Egr‐1 was sufficient to activate transcription of a tyrosine hydroxylase promoter/reporter gene, corroborating the view that the tyrosine hydroxylase gene is a target gene of Egr‐1. Expression of dominant‐negative mutants of Elk‐1 or Egr‐1 impaired TPA‐induced stimulation of a tyrosine hydroxylase promoter/reporter gene transcription. In contrast, dominant‐negative mutants of the transcription factors activating transcription factor (ATF)‐2, ATF4, cAMP response element‐binding protein, c‐Jun and CCAAT/enhancer binding protein (C/EBP) did not change TPA‐induced tyrosine hydroxylase promoter activity, indicating that these proteins are not part of the TPA‐mediated signalling cascade directed towards the tyrosine hydroxylase gene.