Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.30.1 (S1 nuclease)
 3,660 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cell-cell adhesion is critical in the generation of immunologic responses and is dependent upon expression of a variety of cell surface receptors. While intercellular adhesion molecule 1 (ICAM-1), a specific receptor for lymphocyte function-associated antigen 1, is constitutively expressed by some cell types, its de novo or increased expression by various cells has been associated with the initiation of inflammatory responses and appears to be transcriptionally regulated. The 5' region of the human ICAM-1 gene has been cloned and both structurally and functionally analyzed. A 17.3-kilobase genomic clone containing three exonal regions encoding the N-terminal third of the ICAM-1 protein was isolated. A 2.05-kilobase subclone, containing the 5' most exon, was utilized to determine an interferon-gamma-induced transcription initiation site via primer extension and S1 nuclease protection assays. Analysis of the 5'-flanking region revealed consensus sequences for appropriately located basal promoter elements, as well as numerous potential cis-acting enhancer elements. When subcloned into a reporter gene construct, the putative promoter subregion functioned as a potent promoter. However, in accord with biologically observed expression of ICAM-1 in specific cell types, when additional 5'-flanking sequences were included in reporter gene constructs, tissue appropriate repression of transcription was observed.
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PMID:Cloning and characterization of the 5'-transcriptional regulatory region of the human intercellular adhesion molecule 1 gene. 167 59

We previously noted that the initial receptor by which murine osteoclast precursors bind matrix is the integrin alphav beta5 and that granulocyte-macrophage colony-stimulating factor (GM-CSF) decreases expression of this heterodimer by suppressing transcription of the beta5 gene. We herein report cloning of the beta5 integrin gene promoter and identification of a GM-CSF-responsive sequence. A 13-kilobase (kb) genomic fragment containing part of the beta5 gene was isolated by screening a mouse genomic library with a probe derived from the most 5'-end of a murine beta5 cDNA. A combination of primer extension and S1 nuclease studies identifies two transcriptional start sites, with the major one designated +1. A 1-kb subclone containing sequence -875 to + 110 is transcriptionally active in a murine myeloid cell line. This 1-kb fragment contains consensus binding sequences for basal (Sp1), lineage-specific (PU.1), and regulatable (signal transducer and activator of transcription) transcription factors. Reflecting our earlier findings, promoter activity is repressed in transfected myeloid cells treated with GM-CSF. Using deletion mutants, we localized a 109-base pair (bp) promoter region responsible for GM-CSF-inhibited beta5 transcription. We further identified a 19-bp sequence within the 109-bp region that binds GM-CSF-induced nuclear proteins by gel shift/competition assays. Mutation of the 19-bp sequence not only ablates its capacity to bind nuclear proteins from GM-CSF-treated cells, in vitro, but the same mutation, when introduced in the 1-kb promoter, abolishes its ability to respond to GM-CSF treatment. Northern analysis demonstrates that cycloheximide treatment abrogates the capacity of GM-CSF to decrease beta5 mRNA levels. In summary, we have identified a 19-bp cis-element mediating GM-CSF-induced down-regulation of beta5 by a mechanism requiring protein synthesis.
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PMID:Cloning of the murine beta5 integrin subunit promoter. Identification of a novel sequence mediating granulocyte-macrophage colony-stimulating factor-dependent repression of beta5 integrin gene transcription. 988 May 8