One of the mechanisms whereby glucose stimulates insulin gene transcription in pancreatic -cells involves activation of the homeodomain transcription factor PDX1 (pancreatic/duodenal homeobox-1) via a stressactivated pathway involving stress-activated protein kinase 2 (SAPK2, also termed RK/p38, CSBP, and Mxi2). In the present study we show, by Western blotting and electrophoretic mobility shift assay, that in human islets of Langerhans incubated in low glucose (
Pax4 is a paired-box transcription factor that plays an important role in the development of pancreatic L L-cells. Two Pax4 cDNAs were isolated from a rat insulinoma library. One contained the full-length sequence of Pax4. The other, termed Pax4c, was identical to Pax4 but lacked the sequences encoding 117 amino acids at the COOH-terminus. Pax4 was found to inhibit the human insulin promoter through a sequence element, the C2 box, located at 3 3253 to 3 3244, and the islet amyloid polypeptide promoter through a sequence element located downstream of 3 3138. The inhibitory activity of Pax4 was mapped to separate regions of the protein between amino acids 2^230 and 231^349.z 1999 Federation of European Biochemical Societies.
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