Recombinant Mouse NAD (P)H dehydrogenase [quinone] 1 (Nqo1)

Function

Flavin-containing quinone reductase that catalyzes two-electron reduction of quinones to hydroquinones using either NADH or NADPH as electron donors. In a ping-pong kinetic mechanism, the electrons are sequentially transferred from NAD(P)H to flavin cofactor and then from reduced flavin to the quinone, bypassing the formation of semiquinone and reactive oxygen species (By similarity) (PubMed:8999809). Regulates cellular redox state primarily through quinone detoxification. Reduces components of plasma membrane redox system such as coenzyme Q and vitamin quinones, producing antioxidant hydroquinone forms. In the process may function as superoxide scavenger to prevent hydroquinone oxidation and facilitate excretion (By similarity). Alternatively, can activate quinones and their derivatives by generating redox reactive hydroquinones with DNA cross-linking antitumor potential (By similarity). Acts as a gatekeeper of the core 20S proteasome known to degrade proteins with unstructured regions. Upon oxidative stress, interacts with tumor suppressors TP53 and TP73 in a NADH-dependent way and inhibits their ubiquitin-independent degradation by the 20S proteasome (By similarity)

Subcellular Location

Cytoplasm, cytosol

Subunit

Homodimer (PubMed:10706635). Interacts with PDLIM4 isoform 2; this interaction stabilizes PDLIM4 isoform 2 in response to oxidative stress and protects it from ubiquitin-independent degradation by the core 20S proteasome (By similarity). Interacts with TP73 (via SAM domain); this interaction is NADH-dependent, stabilizes TP73 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity). Interacts with TP53; this interaction is NADH-dependent, stabilizes TP53 in response to oxidative stress and protects it from ubiquitin-independent degradation by the 20S proteasome (By similarity)

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• Chen S. et al. Mouse liver NAD(P)H:quinone acceptor oxidoreductase: protein sequence analysis by tandem mass spectrometry, cDNA cloning, expression in Escherichia coli, and enzyme activity analysis. — Protein Sci. (1994)
• Chen S. et al. Molecular basis of the catalytic differences among DT-diaphorase of human, rat, and mouse. — J. Biol. Chem. (1997)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)
• Faig M. et al. Structures of recombinant human and mouse NAD(P)H:quinone oxidoreductases: species comparison and structural changes with substrate binding and release. — Proc. Natl. Acad. Sci. U.S.A. (2000)