Linked Life Data

10373428

Source:http://linkedlifedata.com/resource/pubmed/id/10373428

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
1999-7-15
pubmed:abstractText
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 beta-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 beta-cell line, betaTC3. 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 beta-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 approximately 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18261-70
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Characterization of the mouse sulfonylurea receptor 1 promoter and its regulation.
pubmed:affiliation
Section on Molecular and Cellular Physiology, Diabetes Branch, NIDDK, National Institutes of Health, Bethesda, Maryland 20892-1770, USA.
pubmed:publicationType
Journal Article