Regulation of human prohormone convertase 2 promoter activity by the transcription factor EGR-1

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 2 (PC2) gene...

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Bibliographic Details
Published in:Biochemical journal 1997-11, Vol.328 ( Pt 1) (1), p.69-74
Main Authors: Jansen, E, Ayoubi, T A, Meulemans, S M, Van De Ven, W J
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Cell Line
Cloning, Molecular
COS Cells
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - physiology
Early Growth Response Protein 1
Gene Expression Regulation, Neoplastic - drug effects
Humans
Immediate-Early Proteins
Insulinoma
Molecular Sequence Data
Neoplasm Proteins - genetics
Neurosecretory Systems - metabolism
Pituitary Gland, Anterior
Promoter Regions, Genetic - drug effects
Promoter Regions, Genetic - physiology
Proprotein Convertase 2
Protein Binding - genetics
Sequence Analysis, DNA
Subtilisins - genetics
Transcription Factors - metabolism
Transcription Factors - physiology
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 2 (PC2) gene and established characteristics of the PC2 promoter region. The proximal promoter region is very G+C-rich and does not contain a canonical TATA box or a CAAT box. Transient expression assays with a set of human PC2 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, we show that the transcription factor EGR-1 interacts with two distinct elements within the proximal human PC2 promoter region. Transfection experiments also demonstrate that EGR-1 is able to enhance PC2 promoter activity.
ISSN:0264-6021
1470-8728
DOI:10.1042/bj3280069