0000000000084838

AUTHOR

Thomas Hubrich

showing 4 related works from this author

Tristetraprolin Regulates the Expression of the Human Inducible Nitric-Oxide Synthase Gene

2005

The expression of human inducible NO synthase (iNOS) is regulated both by transcriptional and post-transcriptional mechanisms. Stabilization of mRNAs often depends on activation of p38 mitogen-activated protein kinase (p38 MAPK). In human DLD-1 cells, inhibition of p38 MAPK by the compound 4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1H-imidazole (SB203580) or by overexpression of a dominant-negative p38 MAPKalpha protein resulted in a reduction of human iNOS mRNA and protein expression, whereas human iNOS promoter activity was not affected. An important RNA binding protein regulated by the p38 MAPK pathway and involved in the regulation of the stability of several mRNAs is tr…

ImmunoprecipitationRNA Stabilityp38 mitogen-activated protein kinasesTristetraprolinNitric Oxide Synthase Type IIRNA-binding proteinGene Expression Regulation EnzymologicCell LineImmediate-Early ProteinsTristetraprolinEnzyme StabilityHumansRNA MessengerProtein kinase APharmacologyRegulation of gene expressionbiologyChemistryZinc FingersTransfectionMolecular biologyDNA-Binding ProteinsNitric oxide synthasebiology.proteinMolecular MedicineNitric Oxide SynthaseMolecular Pharmacology
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Involvement of KSRP in the post-transcriptional regulation of human iNOS expression–complex interplay of KSRP with TTP and HuR

2005

We purified the KH-type splicing regulatory protein (KSRP) as a protein interacting with the 3'-untranslated region (3'-UTR) of the human inducible nitric oxide (iNOS) mRNA. Immunodepletion of KSRP enhanced iNOS 3'-UTR RNA stability in in vitro-degradation assays. In DLD-1 cells overexpressing KSRP cytokine-induced iNOS expression was markedly reduced. In accordance, downregulation of KSRP expression increases iNOS expression by stabilizing iNOS mRNA. Co-immunoprecipitations showed interaction of KSRP with the exosome and tristetraprolin (TTP). To analyze the role of KSRP binding to the 3'-UTR we studied iNOS expression in DLD-1 cells overexpressing a non-binding mutant of KSRP. In these ce…

Untranslated regionRNA StabilityTristetraprolinNitric Oxide Synthase Type II610 Medicine & healthRNA-binding proteinBiologyImmediate early proteinArticleGene Expression Regulation EnzymologicELAV-Like Protein 1Immediate-Early ProteinsTristetraprolinCell Line TumorGeneticsHumansRNA Messenger610 Medicine & healthPost-transcriptional regulation3' Untranslated RegionsRegulation of gene expressionMessenger RNAThree prime untranslated regionRNA-Binding ProteinsMolecular biologyDNA-Binding ProteinsELAV ProteinsAntigens SurfaceMutationTrans-ActivatorsCytokinesNitric Oxide SynthaseNucleic Acids Research
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The polypyrimidine tract-binding protein (PTB) is involved in the post-transcriptional regulation of human inducible nitric oxide synthase expression.

2006

Human inducible nitric oxide synthase (iNOS) expression is regulated by transcriptional and post-transcriptional mechanisms. We have recently shown that the multifunctional RNA-binding proteins KH-type splicing regulatory protein and tristetraprolin are critically involved in the post-transcriptional regulation of human iNOS expression. Several reports have shown that KH-type splicing regulatory protein colocalizes with the polypyrimidine tract-binding protein (PTB), and both RNA-binding proteins seem to interact with the same mRNAs. Therefore we analyzed the involvement of PTB in human iNOS expression. In human DLD-1 cells, cytokine incubation necessary to induce iNOS expression did not ch…

Recombinant Fusion ProteinsTristetraprolinGreen Fluorescent ProteinsNitric Oxide Synthase Type IImacromolecular substancesBiologyIn Vitro TechniquesTransfectionenvironment and public healthBiochemistryGene Expression Regulation EnzymologicCell LineCell Line TumorHumansPolypyrimidine tract-binding proteinRNA MessengerEnzyme InhibitorsPromoter Regions GeneticMolecular BiologyPost-transcriptional regulationRegulation of gene expressionMessenger RNAintegumentary systemCarcinomaEpithelial CellsCell BiologyTransfectionMolecular biologyNitric oxide synthaseRNA splicingColonic Neoplasmsbiology.proteinCytokinesRNA InterferenceProtein Processing Post-TranslationalDichlororibofuranosylbenzimidazolePolypyrimidine Tract-Binding ProteinThe Journal of biological chemistry
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Post-transcriptional regulation of the human inducible nitric oxide synthase (iNOS) expression by the cytosolic poly(A)-binding protein (PABP).

2012

Affinity purification using the 3'-untranslated region (3'-UTR) of the human inducible nitric oxide synthase (iNOS) mRNA identified the cytosolic poly(A)-binding protein (PABP) as a protein interacting with the human iNOS 3'-UTR. Downregulation of PABP expression by RNA interference resulted in a marked reduction of cytokine-induced iNOS mRNA expression without changes in the expression of mRNAs coding for the major subunit of the RNA polymerase II (Pol 2A) or β2-microglobuline (β2M). Along with the mRNA also iNOS protein expression was reduced by siPABP-treatment, whereas in the same cells protein expression of STAT-1α, NF-κB p65, or GAPDH was not altered. Reporter gene analyses showed no …

Untranslated regionCancer ResearchSmall interfering RNAFive prime untranslated regionPhysiologyClinical BiochemistryDown-RegulationNitric Oxide Synthase Type IIBiologyBiochemistryPoly(A)-Binding ProteinsCell Line TumorPoly(A)-binding proteinHumansRNA MessengerRNA Processing Post-TranscriptionalPost-transcriptional regulation3' Untranslated RegionsAU-rich elementMessenger RNABinding SitesThree prime untranslated regionMolecular biologyMutationbiology.proteinCytokinesNitric oxide : biology and chemistry
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