Molecular mechanism for activation of superoxide-producing NADPH oxidases

The membrane-integrated protein gp91^phox, existing as a heterodimer with p22^phox, functions as the catalytic core of the phagocyte NADPH oxidase, which plays a crucial role in host defence. The oxidase, dormant in resting cells, becomes activated to produce superoxide, a precursor of microbicidal oxidants, by interacting with the adaptor proteins p47^phox and p67^phox as well as the small GTPase Rac. In the past few years, several proteins homologous to gp91^phox were discovered as superoxide-producing NAD(P)H oxidases (Nox's) in non-phagocytic cells; however, regulatory mechanisms for the novel oxidases have been largely unknown. Current identification of proteins highly related to p47^phox and p67^phox, designated Noxo1 (Nox organizer 1) and Noxa1 (Nox activator 1), respectively, has shed lights on common and distinct mechanisms underlying activations of Nox family oxidases.