REGULATION OF HUMAN PROHORMONE CONVERTASE-2 PROMOTER ACTIVITY BY THE TRANSCRIPTION FACTOR EGR-1

Prohormone convertases are involved in the tissue-specific endoproteol ytic processing of prohormones and neuropeptide precursors within the secretory pathway. In the present study, we have isolated genomic clon es comprising the 5'-terminal region of the human prohormone convertas e 2 (PC2) gene and established characteristics of the PC2 promoter reg ion. The proximal promoter region is very G + C-rich and does not cont ain a canonical TATA box or a CAAT box. Transient expression assays wi th a set of human PC2 gene fragments containing progressive 5' deletio ns demonstrate that the proximal promoter region is capable of directi ng high levels of neuroendocrine-specific expression of reporter gene constructs. In addition, we show that the transcription factor EGR-1 i nteracts with two distinct elements within the proximal human PC2 prom oter region. Transfection experiments also demonstrate that EGR-1 is a ble to enhance PC2 promoter activity.