Cell surface NADH oxidases (ECTO-NOX proteins) with roles in cancer, cellular time-keeping, growth, aging and neurodegenerative diseases.
ECTO-NOX (because of their cell surface location) proteins comprise a family of NAD(P)H oxidases of plants and animals that exhibit both oxidative and protein disulfide isomerase-like activities. The two biochemical activities, hydroquinone [NAD(P)H] oxidation and protein disulfide--thiol interchange alternate, a property unprecedented in the biochemical literature. A tumor-associated ECTO-NOX (tNOX) is cancer-specific and drug-responsive. The constitutive ECTO-NOX (CNOX) is ubiquitous and refractory to drugs. The physiological substrate for the oxidative activity appears to be hydroquinones of the plasma membrane such as reduced coenzyme Q10. ECTO-NOX proteins are growth-related and drive cell enlargement. Also indicated are roles in aging and in neurodegenerative diseases. The regular pattern of oscillations appears to be related to alpha-helix-beta-structure transitions and serves biochemical core oscillator of the cellular biological clock. Period length is independent of temperature (temperature compensated) and synchrony is achieved through entrainment.
Morré
D James
DJ
Department of Medicinal Chemistry and Molecular Pharmacology, Hansen Life Sciences Research Building, West Lafayette, IN, USA. morre@sparky.pharmacy.purdue.edu
Morré
Dorothy M
DM
D000375:Aging; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001683:Biological Clocks; D002455:Cell Division; D002462:Cell Membrane / Q000201:enzymology*; D003067:Coenzymes; D006801:Humans; D008954:Models, Biological; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000096:biosynthesis* / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis* / Q000502:physiology*; D009369:Neoplasms / Q000201:enzymology; D019636:Neurodegenerative Diseases / Q000201:enzymology*; D010100:Oxygen / Q000378:metabolism; D011328:Prions / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013696:Temperature; D013997:Time Factors; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism
D003067:Coenzymes; D009097:Multienzyme Complexes; D011328:Prions; D014451:Ubiquinone; C023107:NADH oxidase; D009247:NADH, NADPH Oxidoreductases; C024989:coenzyme Q10; D010100:Oxygen