Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.28 (chloramphenicol acetyltransferase)
 5,100 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

12(R)-Hydroxy-5,8,14(Z,Z,Z)-eicosatrienoic acid (12(R)-HETrE) is an arachidonic acid metabolite formed by the corneal epithelium of several species, porcine leukocytes, and human and rat epidermal cells. It is a potent, stereospecific proinflammatory and angiogenic factor and its synthesis is increased manyfold in inflamed tissues, e.g. cornea and skin. It is possible that the angiogenic activity of 12(R)-HETrE is due to a direct mitogenic effect on microvessel endothelial cells via yet to be elucidated cellular and molecular mechanisms. In the present study, we demonstrated the ability of 12(R)-HETrE to stimulate the growth of quiescent endothelial cells in a time- and concentration-dependent manner with a maximal effect at 0.1 nM. This effect was highly stereospecific since its enantiomer, 12(S)-HETrE, had no effect within the same concentration range. Northern blot analysis and transient transfection experiments with chloramphenicol acetyltransferase constructs of oncogene promoter regions demonstrated significant increases over control (0.5% fetal calf serum) in c-myc-, c-jun, and c-fos mRNA levels and expression in cells treated with 0.1 nM 12(R)-HETrE. Electrophoretic mobility shift assay of nuclear protein extracts from cells treated with 12(R)-HETrE with specific radiolabeled oligonucleotides corresponding to known transcriptional binding sites, including AP-1, AP-2, SP1, TRE, NF kappa B, TFIID, OKT1, CREB, CTF/NF1, and GRE demonstrated a markedly rapid and specific increase in the binding activity of NF kappa B and to a lesser extent, AP-1. No significant increase was observed in the binding of other transcription factors assayed as compared to control (untreated) cells. Since the protooncogenes (c-fos, c-jun, and c-myc) are immediate early response genes that are implicated in the process of cell proliferation and differentiation, and activation of certain transcription factors, in particular NF kappa B, is associated with the immediate response of the cell to an injury, we propose that 12(R)HETrE's mitogenic and angiogenic activities are mediated, in part, via the activation of NF kappa B and expression of these protooncogenes.
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PMID:Activation of nuclear factor kappa B and oncogene expression by 12(R)-hydroxyeicosatrienoic acid, an angiogenic factor in microvessel endothelial cells. 752 72

The c-myb proto-oncogene product (c-Myb) is a transcriptional activator that can bind to the specific DNA sequences. Although c-Myb also represses an artificial promoter containing the Myb binding sites, natural target genes transcriptionally repressed by c-Myb have not been identified. We have found that the human c-erbB-2 promoter activity is repressed by c-Myb or B-Myb in a chloramphenicol acetyltransferase co-transfection assay. Domain analyses of c-Myb suggested that Myb represses the c-erbB-2 promoter activity by competing with positive regulators of the c-erbB-2 promoter. In in vitro transcription assays, Myb proteins containing only the DNA binding domain could repress c-erbB-2 promoter activity. Two Myb binding sites in the c-erbB-2 promoter were critical for transcriptional repression by c-Myb. One of the two Myb binding sites overlaps the TATA box, and DNase I footprint analyses indicated that c-Myb can compete with TFIID. These results suggest that Myb-induced trans-repression of the c-erbB-2 promoter partly involves competition between Myb and TFIID.
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PMID:c-Myb repression of c-erbB-2 transcription by direct binding to the c-erbB-2 promoter. 772 62

Allelic deletions in the nm23, a metastasis suppressor gene, are known to occur in neuroblastomas, breast and colorectal carcinomas. Down-regulation of nm23 expression has been reported in various rodent and human tumor cells with high metastasis phenotype. Colorectal tumors showed overexpression of nm23. To elucidate the regulatory mechanisms of nm23, we isolated, cloned and sequenced the presumptive regulatory DNA fragment spanning the 5' region of the human nm23-H1 gene. The region's nucleotide sequence shows the presence of motifs typical for transcriptional elements such as TFIID, AP-1 and CTF/NF1. A common transcription initiation site is located at -136 upstream from the first ATG codon in placenta tissue, in breast, colorectal, prostate tumor cell lines and in primary colorectal tumor. Multiple transcription start sites were identified in tumor cell lines and colorectal tumor. When the promoter element was linked to a reporter gene, chloramphenicol acetyltransferase (CAT) and transfected in human 2fTGH cells, strong CAT activity was detected, which also showed that the presence of AP-1 and CTF/NF1 elements are essential for promoter activity. A detailed study of the structure and function of the promoter element of the nm23-H1 gene will help in understanding the regulatory mechanisms of nm23 expression and its role in tumor progression, especially in metastasis.
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PMID:Isolation and characterization of the promoter region of human nm23-H1, a metastasis suppressor gene. 808 95

Second-site revertants from replication-incompetent molecular clones of human immunodeficiency virus (HIV) contain base substitutions adjacent to the TATA motif. The altered TATA box motifs were analyzed for their effect(s) on virus infectivity, long terminal repeat (LTR)-directed expression in transient transfection assays, in vitro RNA synthesis, and assembly of the TFIID-TFIIA preinitiation complex. The revertant TATA boxes accelerated the kinetics of HIV replication when present in the context of an LTR containing a Sp1 mutation (deletion or site specific); no effect was observed on the infectivity of wild-type HIV. In chloramphenicol acetyltransferase assays and in vitro transcription systems, the altered TATA box motifs led to elevated basal levels of RNA synthesis from NF-kappa B- and Sp1-mutagenized and wild-type templates, respectively, but did not increase responsiveness to Tat transactivation. The revertant TATA boxes accelerated the binding of TFIID and TFIIA to the LTR and stabilized their association with the promoter. The revertants did not assemble a more-processive elongation complex. These results suggest that in the context of an impaired enhancer/promoter (viz., three mutated Sp1 elements), a series of HIV revertants emerge which contain LTR alterations that significantly augment basal RNA synthesis. The TATA motif revertants are capable of rescuing the enhancer/promoter defect and sustain virus infectivity.
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PMID:Second-site long terminal repeat (LTR) revertants of replication-defective human immunodeficiency virus: effects of revertant TATA box motifs on virus infectivity, LTR-directed expression, in vitro RNA synthesis, and binding of basal transcription factors TFIID and TFIIA. 815 90