Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:5.99.1.2 (topoisomerase)
 9,166 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The basic helix-loop-helix containing dioxin receptor mediates dioxin signal transduction. The ligand-activated receptor complex binds to specific sequences termed xenobiotic response elements and regulates transcription of target genes such as the gene for cytochrome P450IA1. This study demonstrates that induction of cytochrome P450IA1 and P450IB1 gene expression by a dioxin receptor ligand is repressed by camptothecin, an inhibitor of the topoisomerase I enzyme. However, a transiently transfected reporter construct under control of an xenobiotic response element-containing promoter was not affected by the topoisomerase inhibitor. In agreement with this observation, ligand-dependent activation of the dioxin receptor to its DNA-binding form is not altered by camptothecin as analyzed by electrophoretic mobility shift assay. Moreover, the inhibitory effect of camptothecin cannot be exerted once the P450IA1 gene has been activated. These results imply that topoisomerase I activity is necessary for the primary P450IA1 induction response, possibly involving dioxin-dependent alterations in chromatin structure of the P450IA1 promoter.
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PMID:Differential effects of a topoisomerase I inhibitor on dioxin inducibility and high-level expression of the cytochrome P450IA1 gene. 747 85

Fluoroquinolone resistance in Pseudomonas aeruginosa is mainly attributable to the constitutive expression of the xenobiotic efflux pump and mutation in DNA gyrase or topoisomerase IV. We constructed cells with a double-mutation in gyrA and mexR encoding DNA gyrase and repressor for the mexAB-oprM operon, respectively. The mutant showed 1,024 times higher fluoroquinolone resistance than cells lacking the MexAB-OprM. Cells with a single mutation in gyrA and producing a wild-type level of the MexAB-OprM efflux pump showed 128 times higher fluoroquinolone resistance than cells lacking the MexAB-OprM. In contrast, a single mutation in gyrA or mexR caused only 4 and 64 times higher resistance, respectively. These findings manifested the interplay between the MexAB-OprM efflux pump and the target mutation in fluoroquinolone resistance.
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PMID:High-level fluoroquinolone resistance in Pseudomonas aeruginosa due to interplay of the MexAB-OprM efflux pump and the DNA gyrase mutation. 1215 16

Besides established mechanisms involved in cellular drug resistance including P-glycoprotein overexpression, topoisomerase alterations and xenobiotic detoxification, the hypothesis that proto-oncogene activation might also play a role in cell resistance has been postulated. This hypothesis has been tested by comparing the expression of various proto-oncogenes involved in signal transduction pathways (c-H-ras, c-g-ras, c-mil, c-myc, c-myb, c-fos), as well as the mdr gene and a tumor suppressor gene (p53) in different adriamycin-resistant (acquired or de novo) or sensitive cell lines, The implication of these variations in the process of chemoresistance is discussed.
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PMID:Expression of a tumor-suppressor gene and of various protooncogenes in human and murine adriamycin-resistant and sensitive cell-lines. 2155 66