Cloning of Two Human Thyroid cDNAs Encoding New Members of the NADPH Oxidase Family*

By X. de Deken, Dantong Wang, M. Many, S. Costagliola, F. Libert, G. Vassart, Jacques E. Dumont, F. Miot. Journal of Biological Chemistry, 2000

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Two cDNAs encoding NADPH oxidases and constituting the thyroid H2O2 generating system have been cloned. The strategy of cloning was based on the functional similarities between H2O2 generation in leukocytes and the thyroid, according to the hypothesis that one of the components of the thyroid system would belong to the gp91Phox/Mox1 gene family and display sequence similarities with gp91Phox. Screening at low stringency with a gp91Phox probe of cDNA libraries from thyroid cells in primary culture yielded two distinct human cDNA clones harboring open reading frames of 1551 (ThOX1) and 1548 amino acids (ThOX2), respectively. The encoded polypeptides display 83% sequence similarity and are clearly related to gp91Phox (53 and 47% similarity). The theoretical molecular mass of 177 kDa is close to the apparent molecular mass of 180 kDa of the native corresponding porcine flavoprotein and the protein(s) detected by Western blot in dog and human thyroid. ThOX1 and ThOX2 display sequence similarities of 53% and 61%, respectively, with a predicted protein ofCaenorhabditis elegans over their entire length. They show along their first 500 amino acids a similarity of 43% with thyroperoxidase. The corresponding genes of ThOX1 and ThOX2 are closely linked on chromosome 15q15.3. The dog mRNA expression is thyroid-specific and up-regulated by agents activating the cAMP pathway as is the synthesis of the polypeptides they are coding for. In human thyroid the positive regulation by cAMP is less pronounced. The proteins ThOX1 and ThOX2 accumulate at the apical membrane of thyrocytes and are co-localized with thyroperoxidase.

Subfields: Molecular Biology, Nutrition and Dietetics

View Paper: https://www.semanticscholar.org/paper/07edadf07e05df7308a4760ea42ac9bd97a9d793

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Citations in the corpus

NADPH Oxidases (NOX): An Overview from Discovery, Molecular Mechanisms to Physiology and Pathology (2021, background): “Thus, the identification of NOX1 was quickly followed by the cloning of a new set of homologs: NOX3 [77], NOX4 [78] and NOX5 [79] as well as DUOX1 and DUOX2 (DUal OXidase) [47,48].”
NADPH Oxidases in Cardiovascular Health and Disease (2006, neutral): “Strong expression of both Duoxs was initially identified in the thyroid, with additional weak expression of Duox2 observed in the stomach (64).”
Reactive oxygen species in tumor progression. (2005, background): “(Tumor Necrosis Factor-α), although recent studies have revealed that tumor cells also use NADPH-oxidase to produce oxygen radicals (14, 69).”
Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. (2001, background): “Nox1, gp91phox, Nox3 and Nox4 cluster within a sub-family that is similar to gp91phox, while the Duox's form a separate sub-group, which is also characterized by their larger size and the presence of the peroxidase homology domain (Lambeth et al., 2000; De Deken et al., 2000).”
Hydrogen Peroxide: A Key Messenger That Modulates Protein Phosphorylation Through Cysteine Oxidation (2000, background): “Although it remained unclear for many years whether nonphagocytic cells contain an NADPH oxidase system similar to that of phagocytic cells, several types of NADPH oxidase were recently identified in nonphagocytes (25, 26), and some of these enzyme systems were shown to be responsible for H2O2 produ”
Myeloperoxidase: friend and foe (2005, neutral): “117, 125, 126] and were designated THOX1 and -2 [117].”
Regulation of reactive oxygen species generation in cell signaling (2011, background): “Duox isozymes contain two EF-hands in NH2-terminal region (De Deken et al., 2000).”
Nox proteins in signal transduction (2009, positive): “Originally isolated from the thyroid, they produce the H2O2 that is used to oxidize iodide during thyroid hormone synthesis [10,11].”
Oxidative stress in the placenta (2004, background): “…physiological function of the non-phagocytic Nox genes remains largely unknown, some of these novel Nox isoforms have been shown to generate ROS in reoxygenation models (Caraceni et al. 1995; Zulueta et al. 1995; Souren et al. 1997; Al-Mehdi et al. 1998; Spranger et al. 1998; De Deken et al. 2000).”