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Human Nad(P)H-Quinone Oxidoreductase(2) - Gene Structure, Activity, and Tissue-Specific Expression
Journal of Biological Chemistry. 1994 May 20;269(20) :14502-14508
AbstractHuman NAD(P)H:quinone oxidoreductase, (NQO(2)) gene, 1336 base pairs (bp) of the 5'-flanking region and 165 bp of the 3'- flanking region, have been sequenced. NQO(2) gene is 20 kilobase pairs in length and has seven exons interrupted by six introns as compared to the previously cloned NQO(1) gene which contains six exons. 187 bp of the first exon in the NQO(2) gene are noncoding and are absent in the NQO(1) gene. 92 bp of the second exon in the NQO(2) gene corresponded to the first exon of the NQO(1) gene and so on. The sizes and nucleotide sequences of exons 3-6 are highly conserved between NQO(2) and NQO(1) genes. The last exon in the NQO(2) gene is 1603 bp shorter than the last exon of the NQO(1) gene and encodes for 58 amino acids as compared to 101 amino acids encoded by the NQO(1) gene. This makes NQO(2) protein 43 amino acids shorter than the NQO(1) protein. The high degree of conservation between NQO(2) and NQO(1) gene organization and sequence confirmed that NQO(2) gene encodes for a second member of the NQO gene family in human. Nucleotide sequence analysis of the 5'-flanking region of the NQO(2) gene revealed presence of four SP1 binding sites at positions -214, -170, -106, and -75, a single copy of the antioxidant response element (ARE) at nucleotide -936, and three copies of xenobiotic response element (XRE) at positions -708, -557, and -51. ARE and XRE elements have previously been found in the promoters of the NQO(1) and glutathione S-transferase Ya subunit genes and mediate increases in their expression in response to polycyclic aromatic compounds, phenolic antioxidants, and 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD), respectively. The NQO(2) cDNA-derived protein in monkey kidney COS1 cells efficiently catalyzed nitroreduction of anti-tumor compound CB10-200, an analog of nitrophenylaziridine. Northern blot analysis indicates that NQO(2) gene is expressed in human heart, brain, lung, liver, and skeletal muscle but does not express in placenta. In contrast, the NQO(1) gene was expressed in all human tissues. Large variations were noticed for expression of the NQO(2) and NQO(1) genes among various tissues. 1336 bp of the 5'-flanking region of the NQO(2) gene containing ARE and XRE was found sufficient to increase expression of the CAT gene in response to beta-naphthoflavone and TCDD in transfected human hepatoblastoma (Hep-G2) cells.
NotesEnglish Article NM065 J BIOL CHEM