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 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.
Jansen
E
E
Laboratory for Molecular Oncology, Center for Human Genetics, University of Leuven, Belgium.
Ayoubi
T A
TA
Meulemans
S M
SM
Van De Ven
W J
WJ
D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D051766:Early Growth Response Protein 1; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D017874:Immediate-Early Proteins; D007340:Insulinoma; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D009490:Neurosecretory Systems / Q000378:metabolism; D010903:Pituitary Gland, Anterior; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000502:physiology; D045706:Proprotein Convertase 2; D011485:Protein Binding / Q000235:genetics; D017422:Sequence Analysis, DNA; D013381:Subtilisins / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; D014157:Transcription Factors; D013381:Subtilisins; D045706:Proprotein Convertase 2