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

The epidermal growth factor (EGF) receptor is the functional target of the mitogen EGF and the cellular homolog of the avian erythroblastosis virus erbB oncogene product. Regulation of expression of the proto-oncogene encoding the EGF receptor can be elucidated by studying the structure and function of the gene promoter outside the confines of the cell. Previously, we reported the isolation of the human EGF receptor gene promoter. The promoter is highly GC rich, contains no TATA or CAAT box, and has multiple transcription start sites. An S1 nuclease-sensitive site has now been found 80 to 110 base pairs (bp) upstream from the major in vivo transcription initiation site. Two sets of direct repeat sequences were found in this area; both conform to the motif TCCTCCTCC. When deletion mutations were made in this region of the promoter by using either Bal 31 exonuclease or S1 nuclease, we found that in vivo activity dropped three- to fivefold, on the basis of transient-transfection analysis. Examination of nuclear protein binding to normal and mutated promoter DNAs by gel retardation analysis and DNase I footprinting revealed that two specific factors bind to the direct repeat region but cannot bind to the S1 nuclease-mutated promoter. One of the specific factors is the transcription factor Sp1. The results suggest that these nuclear trans-acting factors interact with the S1 nuclease-sensitive region of the EGF receptor gene promoter and either directly or indirectly stimulate transcription.
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PMID:Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease. 284 30

The promoter region of the epidermal growth factor (EGF) receptor has been identified by in vitro transcription using EGF receptor genomic DNA fragments as template and by primer extension and nuclease S1 mapping using EGF receptor mRNA. Six transcriptional start sites were identified. DNA sequence analysis shows that the promoter region contains neither a "TATA box" nor a "CAAT box," has an extremely high G+C content (88%), and contains five CCGCCC repeats and four (TCC)TCCTCCTCC repeats. This promoter region is situated close to or within a DNase I-hypersensitive site in A431 human epidermoid carcinoma cells, which overproduce the EGF receptor. The EGF receptor gene promoter has some resemblance to the promoter of the hydroxymethylglutaryl-CoA reductase gene and the early promoter of simian virus 40. This similarity may offer a clue to the mechanism by which the receptor gene is regulated.
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PMID:Characterization and sequence of the promoter region of the human epidermal growth factor receptor gene. 299 99

We localized the 5' region of the human gene HER2 in a cloned fragment of genomic DNA. This clone contained exons 1 to 4 of HER2, spanning the coding sequence for the first 191 amino acids. The promoter region of HER2 was identified upstream to exon 1 by nuclease S1 mapping and by a functional assay in which the promoter region drives the expression of a chloramphenicol acetyltransferase gene. The HER2 promoter is different from the promoter of the epidermal growth factor receptor gene (HER1), and the GC boxes which are typical of the promoter of the epidermal growth factor receptor gene are absent from the HER2 promoter. One major and two minor RNA start sites located at nucleotides 178, 244, and 257 upstream to the initiator ATG were identified. The first one is 21 and 70 base pairs downstream from typical TATAA and CAAT boxes, respectively. This indicates that transcription of HER2/neu can be regulated by a mechanism involving a TATA box, as well as by other unidentified regulatory elements.
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PMID:Human HER2 (neu) promoter: evidence for multiple mechanisms for transcriptional initiation. 303 51

An epidermal growth factor (EGF) responsive DNA-binding protein (ERDBP-1) has been identified. It recognizes with high affinity and specificity a specific single-stranded DNA sequence located in the S1 nuclease-sensitive site of the EGF receptor (EGFR) 5' flanking region. The EGF-responsive element, determined by footprint analysis, is located from -364 to -344 (86-106 base pairs upstream from the major in vivo transcription initiation site). The factor does not recognize the antisense DNA sequence or double-stranded DNA of the EGF-responsive element. Three bands were observed by mobility shift assay using nuclear extracts from normal human keratinocytes. UV cross-linking followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed one major band with molecular weight in the range of 121,000 to 128,000. The induction of ERDBP-1 became evident 3 to 4 h after EGF stimulation and remained elevated as long as EGF was present. HL60 cells are devoid of endogenous EGFR and produce no ERDBP-1. Retroviral gene transfer of EGFR into HL60 cells resulted in induction of ERDBP-1 by EGF to levels comparable to those found in human keratinocytes.
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PMID:A sequence-specific single-stranded DNA-binding protein that is responsive to epidermal growth factor recognizes an S1 nuclease-sensitive region in the epidermal growth factor receptor promoter. 811 24