Regulation of the insulin gene by glucose: stimulation of trans-activation potency of human PDX-1 N-terminal domain.
The beta cells in pancreatic islets of Langerhans increase insulin gene transcription in response to glucose. The pancreatic and duodenal homeobox-1 (PDX-1) plays a major role in glucose-induced insulin transcription. We studied the functional regions of the human PDX-1 protein fused to the DNA-binding domain of the transcription factor Gal4. The results indicate that the N-terminal domain of the hPDX-1, required for transactivation (amino acids 1-120) in transfected betaTC6 and HeLa cells, is also regulated by extracellular glucose concentrations in transfected rat islets. Deletion analyses have led to the mapping of two regions within the N terminus that are essential for its trans-activation properties. One sequence spans amino acids 97-120 in transfected islet and HeLa cells or amino acids 77-120 in betaTC6 cells; the other includes the highly conserved B box (amino acids 31-41). We thus present evidence of a glucose effect on hPDX-1 trans-activation activity, in addition to the previously described regulatory effect on its DNA-binding activity.
Shushan
E B
EB
Department of Endocrinology & Metabolism, Hebrew University, Hadassah Medical Center, Jerusalem, Israel.
Cerasi
E
E
Melloul
D
D
D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins; D005656:Fungal Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000502:physiology*; D006367:HeLa Cells; D018398:Homeodomain Proteins; D006801:Humans; D007328:Insulin / Q000235:genetics*; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C052130:GAL4 protein, S cerevisiae; D018398:Homeodomain Proteins; D007328:Insulin; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C084010:pancreatic and duodenal homeobox 1 protein; D005947:Glucose