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J Biol Chem, Vol. 274, Issue 26, 18261-18270, June 25, 1999
From the The ATP-sensitive potassium channels
(K+ATP channels) are heteromultimeric
structures formed by a member of the sulfonylurea receptor (SUR) family
and a member of the inwardly rectifying potassium channel family
(Kir6.x). The K+ATP channels play an essential
role in nutrient-induced insulin secretion from the pancreatic
Characterization of the Mouse Sulfonylurea Receptor 1 Promoter and Its Regulation
,,, and
Section on Molecular and Cellular
Physiology, Diabetes Branch, NIDDK, National Institutes of Health,
Bethesda, Maryland 20892-1770 and the ¶ Department of
Endocrinology, Hospital Clinic, Barcelona 08036, Spain
-cell. We have cloned and characterized the promoter region of the
mouse SUR1 gene, and have shown that it lacks CAAT and TATA boxes or an
initiator element. Studies of transcription initiation in several
tissues showed that there is a common SUR1 promoter in brain, heart,
and pancreas and in the pancreatic -cell line, TC3. The SUR1 gene
uses multiple transcription start sites with the major site located 54 base pairs 5'-upstream of the translation initiation site. Transient transfection experiments in pancreatic -cell lines showed that the
proximal promoter fragment 
84/+54 is sufficient for significant transcriptional activity. The proximal promoter region contains multiple SP1-binding sites, and cotransfection experiments of the SUR1
promoter-luciferase vector with SP1 expression vector in
Drosophila SL2 cells demonstrated a stimulatory effect of
SP1 on SUR1 transcriptional activity. The mobility shift assays
confirmed the interaction of the SP1 transcription factor with the
proximal promoter region of the SUR1 gene. Together, these results
indicate that SP1 may mediate transcription initiation of the SUR1
gene. In addition, we have described the coordinate regulation of the gene expression of both K+ATP channel subunits
by glucocorticoids. SUR1 and Kir6.2 mRNA levels are down-regulated
by ~40-50% in response to glucocorticoid treatment. Interestingly,
the extent of the inhibitory effect as well as the kinetics and
sensitivity are very similar for both mRNAs. Studies of mRNA
turnover demonstrate that glucocorticoids most likely decrease the
transcriptional activity of both SUR1 and Kir6.2 genes since
glucocorticoids failed to affect the stability of each mRNA.
Likewise, the reduction in mRNA levels was correlated with a
decrease in SUR1 and Kir6.2 protein levels.
Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.
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