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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.
Volume 270,
Number 25,
Issue of June 23, pp. 15391-15397, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
HORMONAL REGULATION OF TRANSCRIPTION THROUGH DISTINCT cAMP RESPONSE
ELEMENTS
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