Neuroendocrine-specific expression of the human prohormone convertase 1 gene. Hormonal regulation of transcription through distinct cAMP response elements

Prohormone convertases are involved in the tissue-specific endoproteolytic processing of prohormones and neuropeptide precursors within the secretory pathway. In the present study, we have isolated genomic clones comprising the 5'-terminal region of the human prohormone convertase 1 (PC1) gene...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-06, Vol.270 (25), p.15391-15397
Main Authors: Jansen, E, Ayoubi, T A, Meulemans, S M, Van de Ven, W J
Format: Article
Language:English
Subjects:
Animals
Aspartic Acid Endopeptidases - biosynthesis
Aspartic Acid Endopeptidases - genetics
Base Sequence
Bromocriptine - pharmacology
Cell Line
Cloning, Molecular
Cyclic AMP - metabolism
DNA Primers
Gene Expression Regulation, Enzymologic
Genomic Library
Humans
Luciferases - biosynthesis
Molecular Sequence Data
Neurosecretory Systems - enzymology
Organ Specificity
Promoter Regions, Genetic
Proprotein Convertases
Receptors, Dopamine D2 - biosynthesis
Receptors, Dopamine D2 - metabolism
Recombinant Proteins - biosynthesis
Sequence Deletion
TATA Box
Transcription, Genetic - drug effects
Transfection
Tumor Cells, Cultured
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Summary:Prohormone convertases are involved in the tissue-specific endoproteolytic processing of prohormones and neuropeptide precursors within the secretory pathway. In the present study, we have isolated genomic clones comprising the 5'-terminal region of the human prohormone convertase 1 (PC1) gene and identified and characterized the PC1 promoter region. We found multiple transcription start sites located within a 15-base pair region, 205 base pairs upstream of the translation start codon. The promoter region is not G+C-rich and does not contain a canonical TATA box nor a CAAT box. Transient expression assays with a set of human PC1 gene fragments containing progressive 5' deletions demonstrate that the proximal promoter region is capable of directing high levels of neuroendocrine-specific expression of reporter gene constructs. In addition, the proximal promoter region confers both basal and hormone-regulated promoter activity. Site-specific mutagenesis experiments demonstrate that two closely spaced cAMP response elements within the proximal promoter region direct cAMP-mediated hormonal regulation of transcription of the PC1 gene.
ISSN:0021-9258
DOI:10.1074/jbc.270.25.15391