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)

The synthesis of the glutathione S-transferase Ya subunit is induced in the mammalian liver by chemicals such as phenobarbital and 3-methylcholanthrene. To study the mechanism of this induction, the 5'-flanking region of a mouse glutathione S-transferase Ya subunit gene was fused to the structural gene for chloramphenicol acetyltransferase. The fusion gene was introduced into hepatoma cells for the assay of the expressed acetyltransferase activity. At least two cis-regulatory elements were identified in the 5'-flanking region of the Ya gene: one, responsible for the basal level of expression, is present in the sequence up to -0.2 kb; another, responsible for the inducible expression by aromatic compounds such as beta-naphthoflavone and 3-methylcholanthrene, is located in the sequence from -0.2 kb to -1.6 kb. The inducible element was functional only in cells with normal aromatic compound receptors, and it retained responsiveness to beta-naphthoflavone when transfected into homologous (mouse) or heterologous (rat, human) hepatoma cells. A 150-bp region upstream from the transcription initiation site of the mouse Ya gene was investigated for cis-acting transcriptional elements that are recognized by specific DNA-binding proteins. We show by DNase I foot-printing assays using extracts from liver nuclei that the Ya gene promoter contains, in addition to the TATA and CCAAT boxes, a more distal element that binds a protein which is probably related to the family of nuclear factor 1 (NF1).
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PMID:Regulatory elements controlling the basal and drug-inducible expression of glutathione S-transferase Ya subunit gene. 277 26

Genes of the mouse S locus encoding C4 (the fourth component complement) and Slp (sex-limited protein) show extensive homology but are distinct in their function and regulation. In some mouse strains, such as B10.D2, Slp is androgen regulated, whereas in others, such as B10.W7R, expression of Slp is constitutive. We have previously shown that the B10.W7R strain has multiple Slp genes. In this report, we present the structure of the single C4 and four Slp genes of the B10.W7R S locus and compare the upstream flanking regions by partial sequence analysis and function in transfection assays. Of the four Slp genes, three (Slpw7.A, Slpw7.B, and Slpw7.C) have upstream and promoter regions very similar to those of C4. The fourth Slp gene (Slpw7.D) is instead virtually identical to the androgen-regulated allele (Slpd from the B10.D2 mouse) in upstream regions. In particular, far-upstream sequences from both Slpd and Slpw7.D render the bacterial chloramphenicol acetyltransferase gene hormonally responsive upon transfection into mammary carcinoma cell lines. The upstream sequences between 2 to 3 kilobases of the Slp promoter initiate transcription from multiple sites when fused proximal to the chloramphenicol acetyltransferase gene, and these transcripts are threefold more abundant in the presence of androgen. This behavior is similar for Slpd and Slpw7.D, which suggests that Slpw7.D may be androgen regulated but that this is masked in vivo by constitutive expression of the other Slp genes. Nonhomologous recombination is implicated not only in expanding the copy number of C4 and Slp genes in the B10.W7R mouse but also in creating hybrid genes with regulatory features of C4 and structural features of Slp.
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PMID:Molecular genetics of androgen-dependent and -independent expression of mouse sex-limited protein. 303 33

The binding of beta2 (CD18) integrins on PMN cell membrane to intercellular adhesion molecule (ICAM) counter-receptors on the surface of vascular endothelial cells mediates PMN adhesion to endothelial cells. Neutrophil inhibitory factor (NIF), a 41-kD glycoprotein isolated from the canine hookworm (Ancylostoma caninum), is a beta2 integrin antagonist that inhibits PMN adhesion to endothelial cells. We transferred the NIF gene into CD1 mouse lungs by intravenous injection of cationic liposomes to study the effects of in vivo NIF expression on LPS-induced lung PMN sequestration and the development of lung injury. RT-PCR and Northern blot analysis indicated the lung-selective expression of the NIF transgene, and immunocytochemistry showed prominent NIF expression in pulmonary microvessel endothelial cells. NIF staining was also observed in intraluminal leukocytes present in pulmonary microvessels. This may be the result of NIF binding to leukocytes after its secretion from the transduced lung cells, since there was no evidence of NIF gene expression in circulating leukocytes. Pulmonary vascular NIF expression abrogated the lung tissue PMN uptake and airspace migration of PMN and prevented lung vascular injury (as measured by the lung tissue uptake of [125I]labeled albumin) after the intraperitoneal LPS challenge (200 microg/mouse). Expression of a control protein, chloramphenicol acetyltransferase (CAT), by the same strategy, had no effect on these responses. In vitro studies showed that NIF prevented mouse PMN adhesion consistent with the inhibition of lung uptake after LPS challenge in NIF transgene-expressing mice. We conclude that pulmonary vascular expression of NIF, a specific beta2 integrin- binding protein, is a potentially useful gene transfer strategy in modulating the infiltration of PMN across the alveolar-capillary epithelial barrier and in preventing lung vascular endothelial injury.
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PMID:In vivo expression of neutrophil inhibitory factor via gene transfer prevents lipopolysaccharide-induced lung neutrophil infiltration and injury by a beta2 integrin-dependent mechanism. 961 14