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 5' flanking region of the gene encoding the small intestinal brush-border peptidase aminopeptidase N (APN) was screened for the presence of enhancer regions. A 300 bp region with enhancer activity was identified 2.7 kb upstream of the transcriptional start site which is used in epithelial cells. The enhancer stimulated transcription from a heterologous promoter (the simian virus 40 early promoter) in a position- and orientation-independent manner. The activity of the enhancer is cell-type dependent and it is active in liver (HepG2), intestinal (Caco-2) and myeloid (K562) cells. As the epithelial APN promoter is active in the first two cell-types and the myeloid APN promoter in the last, the results may suggest that the enhancer, through a cooperation with either of the promoters, is important for the tissue-specific expression of APN. A detailed analysis of the enhancer led to the identification of four functionally important regions that are protected against DNase I digestion by Caco-2 nuclear extract. Sequence analysis suggests that two of the regions may interact with members of the Ets transcription factor family (Ets is a transformation-specific protein first discovered in the E26 avian erythroblastosis virus), one region with a CCAAT enhancer-binding protein and one region with Sp1, a transcriptional activator first described as a factor binding to the simian virus 40 early promoter.
 ...
PMID:An enhancer with cell-type dependent activity is located between the myeloid and epithelial aminopeptidase N (CD 13) promoters. 914 67

Caveolin-1 protein has been called a 'conditional tumor suppressor' because it can either suppress or enhance tumor progression depending on cellular context. Caveolin-1 levels are dynamic in non-small-cell lung cancer, with increased levels in metastatic tumor cells. We have shown previously that transactivation of an erythroblastosis virus-transforming sequence (ETS) cis-element enhances caveolin-1 expression in a murine lung epithelial cell line. Based on high sequence homology between the murine and human caveolin-1 promoters, we proposed that ETS proteins might regulate caveolin-1 expression in human lung tumorigenesis. We confirm that caveolin-1 is not detected in well-differentiated primary lung tumors. Polyoma virus enhancer activator 3 (PEA3), a pro-metastatic ETS protein in breast cancer, is expressed at low levels in well-differentiated tumors and high levels in poorly differentiated tumors. Conversely, Net, a known ETS repressor, is expressed at high levels in the nucleus of well-differentiated primary tumor cells. In tumor cells in metastatic lymph node sites, caveolin-1 and PEA3 are highly expressed, whereas Net is now expressed in the cytoplasm. We studied transcriptional regulation of caveolin-1 in two human lung cancer cell lines, Calu-1 (high caveolin-1 expressing) and NCI-H23 (low caveolin-1 expressing). Chromatin immunoprecipitation-binding assays and small interfering RNA experiments show that PEA3 is a transcriptional activator in Calu-1 cells and that Net is a transcriptional repressor in NCI-H23 cells. These results suggest that Net may suppress caveolin-1 transcription in primary lung tumors and that PEA3 may activate caveolin-1 transcription in metastatic lymph nodes.
 ...
PMID:Increased PEA3/E1AF and decreased Net/Elk-3, both ETS proteins, characterize human NSCLC progression and regulate caveolin-1 transcription in Calu-1 and NCI-H23 NSCLC cell lines. 1948 89