Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gastrin gene is transiently expressed in fetal pancreatic islets during islet neogenesis but then switched off after birth when islet cells become fully differentiated. Previous studies identified a cis-regulatory sequence between -109 and -75 in the human gastrin promoter which binds islet cell-specific activators and a nonspecific repressor and thus may act as a molecular switch. The present study identified another cis-regulatory sequence (-163ACACTAAATGAAAGGGCGGGGCAG-140) which bound two islet nuclear proteins in a mutually exclusive manner, as defined by gel shift competition, methylation interference, and DNase I foot-printing assays. The general transactivator Sp1 recognized the downstream GGGCGGGG sequence, but Sp1 binding was prevented when another islet factor bound to the adjacent AT-rich sequence (CTAAATGA). This gastrin AT-rich element is nearly identical to the binding site (ATAAATGA) for the islet-specific transcription factor beta TF-1. However, the gastrin AT-binding factor appeared to differ from beta TF-1 in its gel mobility shift pattern. Transfections of rat insulinoma cells revealed that mutations which blocked binding to the AT-rich element but allowed Sp1 binding up-regulated transcriptional activity. These results suggest that the gastrin AT-binding factor blocks transactivation by Sp1 and may have a role in the repression of gastrin transcription seen at the end of islet differentiation.
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PMID:Mutually exclusive interactions between factors binding to adjacent Sp1 and AT-rich elements regulate gastrin gene transcription in insulinoma cells. 772 90

New compounds, named nuclear aggregates of polyamines, having a molecular mass of 8000, 4800 and < 1000 Da, were found in the nuclear extracts of several replicating cells. Their molecular structure is based on the formation of ionic bonds between polyamine ammonium and phosphate groups. The production of the 4800 Da compound, resulting from the aggregation of five or more < 1000 Da units, was increased in Caco-2 cells treated with the mitogen gastrin. Dissolving single polyamines in phosphate buffer resulted in the in vitro aggregation of polyamines with the formation of compounds with molecular masses identical to those of natural aggregates. After the interaction of the 4800 Da molecular aggregate with the genomic DNA at 37 degrees C, both the absorbance of DNA in phosphate buffer and the DNA mobility in agarose gel increased greatly. Furthermore, these compounds were able to protect the genomic DNA from digestion by DNase I, a phosphodiesterasic endonuclease. Our data indicate that the nuclear aggregate of polyamines interacts with DNA phosphate groups and influence, more efficaciously than single polyamines, both the conformation and the protection of the DNA.
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PMID:Polyamines interact with DNA as molecular aggregates. 1219 10