Regulation of the expression of inducible nitric oxide synthase.
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).
Pautz
Andrea
A
Department of Pharmacology, University Medical Center of the Johannes Gutenberg University Mainz, D-55101 Mainz, Germany.
Art
Julia
J
Hahn
Susanne
S
Nowag
Sebastian
S
Voss
Cornelia
C
Kleinert
Hartmut
H
D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D052247:Nitric Oxide Synthase Type II