6533b824fe1ef96bd12814ae

RESEARCH PRODUCT

Regulation of the expression of inducible nitric oxide synthase

Julia ArtSebastian NowagAndrea PautzSusanne HahnHartmut KleinertCornelia Voss

subject

Gene isoformRegulation of gene expressionCancer ResearchPhysiologyClinical BiochemistryNitric Oxide Synthase Type IIRNA-Binding ProteinsRNARNA-binding proteinBiologyBiochemistryGene Expression Regulation EnzymologicPathophysiologyNitric oxideCell biologyNitric oxide synthasechemistry.chemical_compoundBiochemistrychemistrybiology.proteinHumansRNA MessengerPromoter Regions GeneticTranscription factorTranscription Factors

description

Nitric oxide (NO) generated by the inducible isoform of nitric oxide synthase (iNOS) is involved in complex immunomodulatory and antitumoral mechanisms and has been described to have multiple beneficial microbicidal, antiviral and antiparasital effects. However, dysfunctional induction of iNOS expression seems to be involved in the pathophysiology of several human diseases. Therefore iNOS has to be regulated very tightly. Modulation of expression, on both the transcriptional and post-transcriptional level, is the major regulation mechanism for iNOS. Pathways resulting in the induction of iNOS expression vary in different cells or species. Activation of the transcription factors NF-kappaB and STAT-1alpha and thereby activation of the iNOS promoter seems to be an essential step for the iNOS induction in most human cells. However, at least in the human system, also post-transcriptional mechanisms involving a complex network of RNA-binding proteins build up by AUF1, HuR, KSRP, PTB and TTP is critically involved in the regulation of iNOS expression. Recent data also implicate regulation of iNOS expression by non-coding RNAs (ncRNAs).

https://doi.org/10.1016/j.niox.2010.04.007