Interaction of the transcription factor CREB with pancreatic islet cell-specific enhancer elements.
The cAMP-responsive element (CRE)-binding transcription factor CREB confers basal as well as cAMP- and calcium-induced transcription. Activation of CREB occurs by phosphorylation on serine-119 stimulating its transactivating potency. However, the regulation of CREB-DNA binding by posttranslational modification is not established. In this study, using binding and functional assays, the interaction of CREB with pancreatic islet cell-specific enhancer elements of the rat somatostatin (SMS-UE), glucagon (Glu-G3) and insulin I genes (Ins-E1) was investigated, which share a functional regulatory sequence, PISCES, with islet-specific activity. CREB bound to the SMS-UE. Bacterially expressed recombinant CREB bound equally well to the SMS-UE and to the somatostatin CRE. However, cellular CRE-binding proteins with CREB-like immunoreactivity recognized the SMS-UE markedly less well than the somatostatin CRE suggesting the existence of a posttranslational modification of CREB that alters its binding specificity.
Diedrich
T
T
Department of Biochemical Pharmacology, University of Göttingen, Germany.
Knepel
W
W
D000818:Animals; D001483:Base Sequence; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D005934:Glucagon / Q000235:genetics; D007328:Insulin / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013004:Somatostatin / Q000235:genetics
D017362:Cyclic AMP Response Element-Binding Protein; D007328:Insulin; D011993:Recombinant Fusion Proteins; D013004:Somatostatin; D005934:Glucagon