High impact information on NOXO1

• Plasma membrane targeting of Noxa1 depends on Noxo1, through tail-to-tail interactions between these proteins [1].
• When Nox1 is co-expressed along with its regulatory subunits NOXO1 and NOXA1, significant ROS generation is seen [2].
• We previously showed that the initial suppression of the oxidase response of chemoattractant-stimulated adherent neutrophils is mediated via inhibition of Vav1-induced activation of the NADPH oxidase regulatory GTPase Rac2 by adhesion signals [3].
• Unexpectedly, Nox3 was strongly activated by NOXO1 in the absence of NOXA1 or p67(phox) [4].
• A point mutation in the PX domain of holo-NOXO1 decreases lipid binding resulting in cytosolic localization and also inhibits NOXO1-activation of Nox1 [5].

Biological context of NOXO1

• 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 [6].

Anatomical context of NOXO1

• This localization of NOXO1 is dictated by its PX domain, since this domain but not the remainder of the molecule localizes to membranes [5].
• Here we describe an alternative splicing form of Noxo1, Noxo1gamma, which is expressed in the testis and fetal brain [7].
• Electropermeabilized HeLa cells, ectopically expressing Nox1, Noxo1, and Noxa1, produce superoxide in a GTP-dependent manner, which is abrogated by expression of a mutant Noxa1(R103E), defective in Rac binding [8].
• Here, we show that Noxo1 supports superoxide production in a cell-free system for gp91(phox)/Nox2 activation by arachidonic acid [9].

Associations of NOXO1 with chemical compounds

• Interaction between the SH3 domains and C-terminal proline-rich region in NADPH oxidase organizer 1 (Noxo1) [9].
• NADPH oxidase organizer 1 (Noxo1), harboring a PX domain, two SH3 domains, and a proline-rich region (PRR), participates in activation of superoxide-producing Nox-family NADPH oxidases [9].

Other interactions of NOXO1

• These results suggest that the formation of the complex consisting of Nox1, betaPix, and NoxO1 is likely to be a critical step in EGF-induced ROS generation [10].

Analytical, diagnostic and therapeutic context of NOXO1

• Immunoprecipitation experiments demonstrated a complex containing Rac1(G12V), NOXO1, NOXA1, and Nox1 [2].

References