Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P51532 (transcriptional activator)
 6,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The migration-inducing gamma2 chain of laminin-5, one of the best known invasion markers, is strongly overexpressed in disseminating and infiltrating tumor cells at the invasive front of colorectal carcinomas. The same tumor cells show nuclear accumulation of the oncoprotein beta-catenin, which together with T-cell factor-DNA-binding proteins, functions as transcriptional activator of genes involved in tumor progression. Here we show that beta-catenin activates the human laminin-5 gamma2 gene through two T-cell factor-binding elements in a synergistic manner together with hepatocyte growth factor and conclude that laminin-5 gamma2 is another important target gene of nuclear beta-catenin during tumor progression.
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PMID:Expression of the invasion factor laminin gamma2 in colorectal carcinomas is regulated by beta-catenin. 1171 33

Hepatocyte growth factor (HGF) receptor, the product of the c-met protooncogene, is transcriptionally regulated by a wide variety of cytokines as well as extracellular environmental cues. In this report, we demonstrate that c-met expression was significantly suppressed by oxidative stress. Treatment of mouse renal inner medullary collecting duct epithelial cells with 0.5 mM H(2)O(2) inhibited c-met mRNA and protein expression, which was concomitant with induction of Egr-1 transcription factor. Ectopic expression of Egr-1 in renal epithelial cells markedly inhibited endogenous c-met expression in a dose-dependent fashion, suggesting a causative effect of Egr-1 in mediating c-met suppression. The cis-acting element responsible for H(2)O(2)-induced c-met inhibition was localized at nucleotide position -223 to -68 of c-met promoter, in which reside an imperfect Egr-1 and three Sp1-binding sites. Egr-1 markedly suppressed c-met promoter activity but did not directly bind to its cis-acting element in the c-met gene. Induction of Egr-1 by oxidative stress attenuated the binding of Sp1 to its cognate sites, but it did not affect Sp1 abundance in renal epithelial cells. Immunoprecipitation uncovered that Egr-1 physically interacted with Sp1 by forming the Sp1/Egr-1 complex, which presumably resulted in a decreased availability of unbound Sp1 as a transcriptional activator for the c-met gene. Thus it appears that inhibition of c-met expression by oxidative stress is mediated by the interplay between Sp1 and Egr-1 transcription factors. Our findings reveal a novel transcriptional regulatory mechanism by which Egr-1 sequesters Sp1 as a transcriptional activator of c-met via physical interaction.
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PMID:Suppression of HGF receptor gene expression by oxidative stress is mediated through the interplay between Sp1 and Egr-1. 1256 82

Insulin transcription factor MafA is unique in being exclusively expressed at the secondary and principal phase of insulin-expressing cell production during pancreas organogenesis and is the only transcriptional activator present exclusively in islet beta-cells. Here we show that ectopic expression of MafA is sufficient to induce a small amount of endogenous insulin expression in a variety of non-beta-cell lines. Insulin mRNA and protein expression was induced to a much higher level when MafA was provided with two other key insulin activators, pancreatic and duodenal homeobox (PDX-1) and BETA2. Potentiation by PDX-1 and BETA2 was entirely dependent upon MafA, and MafA binding to the insulin enhancer region was increased by PDX-1 and BETA2. Treatment with activin A and hepatocyte growth factor induced even larger amounts of insulin in AR42J pancreatic acinar cells, compared with other non-beta endodermal cells. The combination of PDX-1, BETA2, and MafA also induced the expression of other important regulators of islet beta-cell activity. These results support a critical role of MafA in islet beta-cell function.
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PMID:MafA regulates expression of genes important to islet beta-cell function. 1763 40