rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2005-11-3
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pubmed:abstractText |
Tetrahydrobiopterin is an essential cofactor for the phenylalanine, tyrosine and tryptophan hydroxylases, and the family of nitric oxide synthases. The initial and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin is GTP cyclohydrolase I. The proximal promoter of the human GTP cyclohydrolase I gene contains the sequence motif 5'-TGACGCGA-3', resembling a cAMP response element (CRE). The objective of this study was to analyze the regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper (bZIP) transcription factors. A constitutively active mutant of the cAMP response element binding (CREB) protein strongly stimulated GTP cyclohydrolase I promoter activity, indicating that the CRE in the context of the GTP cyclohydrolase I gene is functional. Likewise, GTP cyclohydrolase I promoter/luciferase gene transcription was stimulated following nuclear expression of the catalytic subunit of cAMP-dependent protein kinase. Constitutively active mutants of activating transcription factor 2 (ATF2) and c-Jun additionally stimulated GTP cyclohydrolase I promoter activity, but to a lesser extent than the constitutively active CREB mutant. The fact that stress-activated protein kinases target the GTP cyclohydrolase I gene was corroborated by expression experiments involving p38 and MEKK1 protein kinases. We conclude that signaling pathways involving either the cAMP-dependent protein kinase or stress-activated protein kinases converge to the GTP cyclohydrolase I gene. Hence, enzymatic reactions that require tetrahydrobiopterin as cofactor are therefore indirectly controlled by signaling cascades involving the signal-responsive transcription factors CREB, c-Jun, and ATF2.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ATF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Activating Transcription Factor 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Single-Stranded,
http://linkedlifedata.com/resource/pubmed/chemical/DNA enzyme ED5,
http://linkedlifedata.com/resource/pubmed/chemical/GTP Cyclohydrolase,
http://linkedlifedata.com/resource/pubmed/chemical/Luciferases,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-jun,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0730-2312
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pubmed:author |
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pubmed:copyrightInfo |
2005 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
96
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1003-20
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16149046-Activating Transcription Factor 2,
pubmed-meshheading:16149046-Amino Acid Sequence,
pubmed-meshheading:16149046-Base Sequence,
pubmed-meshheading:16149046-Catalysis,
pubmed-meshheading:16149046-Catalytic Domain,
pubmed-meshheading:16149046-Cell Line, Tumor,
pubmed-meshheading:16149046-Cell Nucleus,
pubmed-meshheading:16149046-Cells, Cultured,
pubmed-meshheading:16149046-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:16149046-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:16149046-DNA, Single-Stranded,
pubmed-meshheading:16149046-GTP Cyclohydrolase,
pubmed-meshheading:16149046-Gene Expression Regulation,
pubmed-meshheading:16149046-Genes, Reporter,
pubmed-meshheading:16149046-Genetic Vectors,
pubmed-meshheading:16149046-Humans,
pubmed-meshheading:16149046-Leucine Zippers,
pubmed-meshheading:16149046-Luciferases,
pubmed-meshheading:16149046-MAP Kinase Kinase Kinase 1,
pubmed-meshheading:16149046-Models, Genetic,
pubmed-meshheading:16149046-Molecular Sequence Data,
pubmed-meshheading:16149046-Mutation,
pubmed-meshheading:16149046-Plasmids,
pubmed-meshheading:16149046-Promoter Regions, Genetic,
pubmed-meshheading:16149046-Protein Structure, Tertiary,
pubmed-meshheading:16149046-Proto-Oncogene Proteins c-jun,
pubmed-meshheading:16149046-Signal Transduction,
pubmed-meshheading:16149046-Transcription, Genetic,
pubmed-meshheading:16149046-Transcription Factors,
pubmed-meshheading:16149046-Transcriptional Activation,
pubmed-meshheading:16149046-Transfection,
pubmed-meshheading:16149046-Tumor Necrosis Factor-alpha,
pubmed-meshheading:16149046-Up-Regulation,
pubmed-meshheading:16149046-p38 Mitogen-Activated Protein Kinases
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pubmed:year |
2005
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pubmed:articleTitle |
Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors.
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pubmed:affiliation |
Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, Homburg, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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