Search results for "Prenylation"

showing 3 items of 23 documents

Inhibition of small G proteins of the Rho family by statins orClostridium difficiletoxin B enhances cytokine-mediated induction of NO synthase II

2000

In order to investigate the involvement of Ras and/or Rho proteins in the induction of the inducible isoform of nitric oxide synthase (NOS II) we used HMG-CoA reductase inhibitors (statins) and Clostridium difficile toxin B (TcdB) as pharmacological tools. Statins indirectly inhibit small G proteins by preventing their essential farnesylation (Ras) and/or geranylgeranylation (Rho). In contrast, TcdB is a glucosyltransferase and inactivates Rho-proteins directly. Human A549/8- and DLD-1 cells as well as murine 3T3 fibroblasts were preincubated for 18 h with statins (1–100 μM) or TcdB (0.01–10 ng ml−1). Then NOS II expression was induced by cytokines. NOS II mRNA was measured after 4–8 h by R…

rho GTP-Binding ProteinsG proteinBacterial ToxinsMevalonic AcidNitric Oxide Synthase Type IISmall G ProteinClostridium difficile toxin BBiologyGene Expression Regulation EnzymologicMiceGeranylgeranylationBacterial ProteinsPolyisoprenyl PhosphatesPrenylationGTP-Binding ProteinsGene expressionAtorvastatinTumor Cells CulturedAnimalsHumansDrug InteractionsPyrrolesLovastatinPromoter Regions GeneticPharmacology3T3 CellsTransfectionMolecular biologyHeptanoic AcidsEnzyme InductionPapersCytokinesHydroxymethylglutaryl-CoA Reductase InhibitorsNitric Oxide SynthaseSignal transductionBritish Journal of Pharmacology
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Rho GTPases: Promising Cellular Targets for Novel Anticancer Drugs

2006

Ras-homologous (Rho) GTPases play a pivotal role in the regulation of numerous cellular functions associated with malignant transformation and metastasis. Rho GTPases are localized at membranes and become activated upon stimulation of cell surface receptors. In their GTP-bound (=active) state, Rho proteins bind to effector proteins, thereby triggering specific cellular responses. Members of the Rho family of small GTPases are key regulators of actin reorganization, cell motility, cell-cell and cell-extracellular matrix (ECM) adhesion as well as of cell cycle progression, gene expression and apoptosis. Each of these functions is of importance for the development and progression of cancer. Fu…

rho GTP-Binding ProteinsPharmacologyCancer ResearchRHOAbiologyChemistryRHOBFarnesyltransferaseAntineoplastic AgentsRAC1GTPaseCell biologyCell Transformation NeoplasticOncologyPrenylationDrug Resistance NeoplasmTumor progressionDrug Discoverybiology.proteinAnimalsHumansEnzyme InhibitorsLipid modificationMutagensCurrent Cancer Drug Targets
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Inhibition of Protein Isoprenylation Impairs Rho-Regulated Early Cellular Response to Genotoxic Stress

2000

Activation of c-Jun N-terminal kinases (JNKs) and nuclear factor-kappaB (NF-kappaB) are early cellular responses to genotoxic stress involved in the regulation of gene expression. Pretreatment of cells with the hydroxymethyl glutaryl-CoA reductase inhibitor lovastatin blocked stimulation of JNK1 activity by UV irradiation and by treatment with the alkylating compound methyl methanesulfonate but did not affect activation of extracellular signal-regulated kinase 2 by UV light. Lovastatin also attenuated UV-induced degradation of the NF-kappaB inhibitor IkappaBalpha. The effects of lovastatin on UV-triggered stimulation of JNK1 as well as on IkappaBalpha degradation were reverted by cotreatmen…

rho GTP-Binding ProteinsProtein PrenylationStimulationClostridium difficile toxin BCHO CellsGenotoxic StressBiologychemistry.chemical_compoundCricetinaemedicineAnimalsHumansMitogen-Activated Protein Kinase 8LovastatinPharmacologyMutagenicity TestsKinaseFarnesyltransferase inhibitorNF-kappa BMethyl methanesulfonateCell biologyIκBαchemistryMolecular MedicineLovastatinHydroxymethylglutaryl-CoA Reductase InhibitorsMitogen-Activated Protein KinasesHeLa CellsSignal Transductionmedicine.drugMolecular Pharmacology
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