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)

Many viral oncogenes encode protein-tyrosine kinase activities. However, important in vivo substrates of these enzymes have yet to be identified. Recently, type I topoisomerases were shown to be in vitro substrates for two tyrosine kinases. Following tyrosine phosphorylation, topoisomerase I activity was reduced 10-fold (Tse-Dinh et al. Nature 312: 785-786, 1984). To determine whether topoisomerase I activity was modulated by tyrosine phosphorylation in vivo, we have measured topoisomerase I activity in nuclear lysates prepared from both normal fibroblasts and cells transformed by two different viral oncogenes (v-abl, v-src). Under a variety of experimental conditions, we have found no evidence to support the notion that type I topoisomerase activity is modulated by tyrosine phosphorylation in vivo.
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PMID:A comparison of topoisomerase I activity in normal and transformed cells. 301 75

Hybridization with cDNA arrays was used to obtain expression profiles of 214 protein-tyrosine kinase, protein-tyrosine phosphatase, dual-specific phosphatase, and other genes for kidney carcinomas (KC) and normal kidney tissues of 34 patients and for seven carcinoma cell lines. Computer analysis revealed three clusters of genes coexpressed in KC. A proliferating-cell gene cluster included MET, VIM, MYC, TOP2A, PCNA, etc. A neoangiogenesis and blood-cell gene cluster included LCK, HCK, FGR, MMP9, CSFR1, VEGF, FLT1, and KDR. A cluster corresponding to normal, differentiated kidney cells included ERBB2 (HER2) for receptor protein-tyrosine kinase, several phosphatase genes (PTPRE, PTPRB, DUSP9), and EGF. The results suggested that MET, DUSP9, PCNA, TOP2A, and VIM may serve as diagnostic and prognostic markers in KC. Tubulin and topoisomerase II were assumed to be promising targets for cell proliferation inhibitors in KC.
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PMID:[Molecular portrait of human kidney carcinomas: the gene expression profiling of protein-tyrosine kinases and tyrosine phosphatases which controlled regulatory signals in the cells]. 1206 34

Genistein is a phytoestrogen that has shown potential as a chemotherapeutic agent, which acts by inhibiting protein-tyrosine kinase and topoisomerase II enzymes. These particular enzymes are crucial for cellular proliferation. The goal of this study was to evaluate the effect of genistein concentration (0.5, 0.05 or 0.005 mg/mL) on Hep-2 cells functional capacity. Specifically, to evaluate cellular number, protein, damage and morphology at 24, 48, and 72 hours phases. Data obtained from this study revealed that cell numbers were significantly reduced in low and medium concentrations after 24hrs, and cell numbers appeared to rebound at 48 and 72hrs in an inverse fashion. This data suggests continuous administration of the drug at therapeutic levels would serve as a better chemotherapeutic agent. Cellular damage was not evidenced and suggesting that the drug did not target the cellular membrane site. Morphological changes such as anucleation were seen at 24 hrs in all doses suggesting that genistein targets the genome directly. Interestingly, cellular function was able to recover in the lower doses of genistein treatment indicating cellular metabolism of the drug. Also, this information suggests that genistein mode of action by targeting enzymatic activity, as opposed to causing alterations within the cellular membrane, leading to leakage of cellular contents and ultimately cellular death since the membrane did not show evidence of lipid peroxidation.
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PMID:The effects of genistein concentrations on Hep-2 cellular function. 1585 Jan 5