Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors | |
Al Sarraj, J. ; Vinson, C. ; Han, J. H. ; Thiel, G. ; Han JH(韩家淮) | |
2005 | |
关键词 | ATF2 CREB c-Jun MEKK1 p38 protein kinase Egr-1 promoter TNF alpha promoter |
英文摘要 | 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 1. 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. |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://dspace.xmu.edu.cn/handle/2288/65797] ![]() |
专题 | 生命科学-已发表论文 |
推荐引用方式 GB/T 7714 | Al Sarraj, J.,Vinson, C.,Han, J. H.,et al. Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors[J],2005. |
APA | Al Sarraj, J.,Vinson, C.,Han, J. H.,Thiel, G.,&韩家淮.(2005).Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors.. |
MLA | Al Sarraj, J.,et al."Regulation of GTP cyclohydrolase I gene transcription by basic region leucine zipper transcription factors".(2005). |
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