Soluble Regulatory Proteins for Activation of NOX Family NADPH Oxidases

NOX family NADPH oxidases deliberately produce reactive oxygen species and thus contribute to a variety of biological functions. Of seven members in the human family, the three oxidases NOX2, NOX1, and NOX3 form a heterodimer with p22^phox and are regulated by soluble regulatory proteins: p47^phox, its related organizer NOXO1; p67^phox, its related activator NOXA1; p40^phox; and the small GTPase Rac. Activation of the phagocyte oxidase NOX2 requires p47^phox, p67^phox, and GTP-bound Rac. In addition to these regulators, p40^phox plays a crucial role when NOX2 is activated during phagocytosis. On the other hand, NOX1 activation prefers NOXO1 and NOXA1, although Rac is also involved. NOX3 constitutively produces superoxide, which is enhanced by regulatory proteins such as p47^phox, NOXO1, and p67^phox. Here we describe mechanisms for NOX activation with special attention to the soluble regulatory proteins.