Alternative mRNA splice forins 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 gp9lphox homologs Nox1 and Nox3. Herein, we report four splice forms of human NOXO1. NOXO1 beta is the major mRNA splice form in human colon and fetal liver while NOXO1-gamma 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 NOXO1 beta and NOXO1 gamma bound these lipids with the same specificity and affinity. NOXO1 beta and NOXO1 gamma both activated Nox1, but NOXO1 gamma showed a poorer ability to activate Nox3 compared with NOXO1 beta. These data suggest different tissue localizations and functions for NOXO1 beta and NOXO1 gamma in regulating Nox family members. (c) 2005 Elsevier B.V. All rights reserved.