Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-11-3
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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...
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0730-2312
pubmed:author
pubmed:copyrightInfo
2005 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1003-20
pubmed:dateRevised
2009-11-19
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
pubmed:year
2005
pubmed:articleTitle
Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors.
pubmed:affiliation
Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, Homburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't