Alternative mRNA splice forms of NOXO1: differential tissue expression and regulation of Nox1 and Nox3.
The activity of gp91phox, the catalytic subunit of the superoxide-generating respiratory burst oxidase, is stimulated by the regulatory subunits p47phox, p67phox and the small GTPase Rac. Novel homologs of p47phox and p67phox (NOXO1 and NOXA1, respectively) were recently identified and are implicated in the regulation of the gp91phox homologs Nox1 and Nox3. Herein, we report four splice forms of human NOXO1. NOXO1beta is the major mRNA splice form in human colon and fetal liver while NOXO1gamma was the majority species in testis. Neither the alpha nor delta forms were expressed in significant amounts in any tissue tested. Splice forms were generated by alternative splicing of the two ends of exon 3 of the NOXO1 gene, and resulted in differences in the PX domain. The PX domain is known to bind inositol lipids, but the expressed, purified PX domains from NOXO1beta and NOXO1gamma bound these lipids with the same specificity and affinity. NOXO1beta and NOXO1gamma both activated Nox1, but NOXO1gamma showed a poorer ability to activate Nox3 compared with NOXO1beta. These data suggest different tissue localizations and functions for NOXO1beta and NOXO1gamma in regulating Nox family members.
Cheng
Guangjie
G
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Lambeth
J David
JD
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics*; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D002460:Cell Line; D003106:Colon / Q000378:metabolism; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005796:Genes / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007438:Introns; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases / Q000235:genetics; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D018076:DNA, Complementary; D008565:Membrane Proteins; C476419:NOXO1 protein, human; C472287:Noxo1 protein, mouse; D020033:Protein Isoforms; D011506:Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D019255:NADPH Oxidases; C402799:NOX1 protein, human; C000614711:NOX1 protein, mouse; C431570:Nox3 protein, human; C484511:Nox3 protein, mouse; D005982:Glutathione Transferase