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 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.
Jansen
E
E
Laboratory for Molecular Oncology, University of Leuven, Belgium.
Ayoubi
T A
TA
Meulemans
S M
SM
Van de Ven
W J
WJ
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis* / Q000235:genetics*; D001483:Base Sequence; D001971:Bromocriptine / Q000494:pharmacology; D002460:Cell Line; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism*; D017931:DNA Primers; D015971:Gene Expression Regulation, Enzymologic; D015698:Genomic Library; D006801:Humans; D008156:Luciferases / Q000096:biosynthesis; D008969:Molecular Sequence Data; D009490:Neurosecretory Systems / Q000201:enzymology*; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D043484:Proprotein Convertases; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis; D017384:Sequence Deletion; D016385:TATA Box; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D017448:Receptors, Dopamine D2; D011994:Recombinant Proteins; D001971:Bromocriptine; D000242:Cyclic AMP; D008156:Luciferases; D043484:Proprotein Convertases; D016282:Aspartic Acid Endopeptidases