Inhibitory effect of Pax4 on the human insulin and islet amyloid polypeptide (IAPP) promoters

Pax4 is a paired-box transcription factor that plays an important role in t he development of pancreatic beta-cells. Two Pax4 cDNAs were isolated from a rat insulinoma library. One contained the full-length sequence of Pax4, T he other, termed Pax4c, was identical to Pax4 but lacked the sequences enco ding 117 amino acids at the COOH-terminus, Pax4 was found to inhibit the hu man insulin promoter through a sequence element, the C2 box, located at -25 3 to -244, and the islet amyloid poly peptide promoter through a sequence e lement located downstream of -138, The inhibitory activity of Pax4 was mapp ed to separate regions of the protein between amino acids 2-230 and 231-349 . (C) 1999 Federation of European Biochemical Societies.