[V-1, a catecholamine biosynthesis regulatory protein, enhances GTP cyclohydrolase I gene transcription in a cAMP-responsive element dependent manner].
Nihon Yakurigaku Zasshi
; 120(1): 82P-84P, 2002 Nov.
Article
em Ja
| MEDLINE
| ID: mdl-12491788
ABSTRACT
V-1 is a 12 kDa protein containing 2.5 copies of the ankyrin repeat, which has been demonstrated to be required for protein-protein interactions. Recently we have for the first time reported that stable overexpression of V-1 enhances mRNA expression of catecholamine synthesizing enzymes in PC12D cells, and as a result, catecholamine production is upregulated. GTP cyclohydrolase I (GCH) is the enzyme in the first and rate-limiting step for the biosynthesis of tetrahydrobiopterin (BH4) which is an essential cofactor for tyrosine hydroxylase. In the present study, to examine further the function of V-1 in control of the BH4 biosynthesis, we assayed BH4 content and GCH enzyme activity in V-1-overexpressing PC12D cell clones. It was shown that both BH4 content and GCH enzyme activity were increased in V-1-verexpressing PC12D cell clones. It was also revealed that V-1-overexpression caused augmentation of both the GCH protein and mRNA expression and the cAMP-responsive element (CRE) dependent transcription. Furthermore, promoter analysis showed an increased activity in the construct with 150 bp of promoter region of the human GCH gene in the V-1-overexpressing clones. These results suggest that V-1 promotes GCH gene expression via a CRE-dependent transcription to positively control the BH4 biosynthesis in catecholaminergic cells.
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Base de dados:
MEDLINE
Assunto principal:
Transcrição Gênica
/
Biopterinas
/
Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico
/
Peptídeos e Proteínas de Sinalização Intercelular
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GTP Cicloidrolase
/
Proteínas do Tecido Nervoso
Limite:
Animals
Idioma:
Ja
Revista:
Nihon Yakurigaku Zasshi
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Japão