NQO1 gene

The NQO1 gene belongs to the family of NAD(P)H dehydrogenase genes (quinones) and encodes a cytoplasmic reductase. The NQO1 FAD-binding protein forms homodimers and reduces quinones to hydroquinones. The enzymatic activity of this protein prevents the one-electron reduction of quinones, which leads to the formation of radical species. Mutations in this gene have been associated with tardive dyskinesia (TD), increased risk of hematotoxicity after benzene exposure and susceptibility to various cancers. Altered expression of this protein has been observed in many tumors and is also associated with Alzheimer's disease (AD).

The encoded NQO1 protein is a flavin-containing quinone reductase that catalyzes the two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a kinetic ping-pong mechanism, electrons are transferred sequentially from NAD(P)H to the flavin cofactor and then from the reduced flavin to the quinone, bypassing the formation of semiquinone and reactive oxygen species (Chen S et al. 1997). NQO1 regulates the cellular redox state mainly through quinone detoxification. Alternatively, it can activate quinones and their derivatives by generating redox-reactive hydroquinones with DNA-crosslinking antitumor potential (Chen S et al. 1997). Acts as a gatekeeper of the 20S core proteasome, which is known to degrade proteins with unstructured regions. Under oxidative stress, interacts with the tumor suppressors TP53 and TP73 in an NADH-dependent manner and inhibits their ubiquitin-independent degradation by the 20S proteasome (Asher G et al. 2005).

1. Asher G et al. (2005) A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73. Genes Dev 19:316-321.
2. Chen S et al. (1997) Molecular basis of the catalytic differences among DT-diaphorase of human, rat, and mouse. J Biol Chem 272:1437-1439.