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.
Department of Medicinal Chemistry and Molecular Pharmacology, Hansen Life Sciences Research Building, West Lafayette, IN, USA. morre@sparky.pharmacy.purdue.edu
D James
DJ
Morré
Dorothy M
DM
Morré
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