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 Noxal (Nox activator 1), respectively, has shed lights on common and distinct mechanisms underlying activations of Nox family oxidases.