{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:28:45Z","timestamp":1791343725609,"version":"4.3.1"},"reference-count":18,"publisher":"National Academy of Sciences","issue":"25","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1996,12,10]]},"abstract":"<jats:p>\n                    Twenty-four base pairs of the human antioxidant response element\n (hARE) are required for high basal transcription of the NAD(P)H:quinone\n oxidoreductase\n                    <jats:sub>1<\/jats:sub>\n                    (NQO\n                    <jats:sub>1<\/jats:sub>\n                    ) gene and its induction\n in response to xenobiotics and antioxidants. hARE is a unique\n cis-element that contains one perfect and one imperfect AP1 element\n arranged as inverse repeats separated by 3 bp, followed by a \u201cGC\u201d\n box. We report here that Jun, Fos, Fra, and Nrf nuclear transcription\n factors bind to the hARE. Overexpression of cDNA derived combinations\n of the nuclear proteins Jun and Fos or Jun and Fra1 repressed\n hARE-mediated chloramphenicol acetyltransferase (CAT) gene expression\n in transfected human hepatoblastoma (Hep-G2) cells. Further experiments\n suggested that this repression was due to overexpression of c-Fos and\n Fra1, but not due to Jun proteins. The Jun (c-Jun, Jun-B, and Jun-D)\n proteins in all the possible combinations were more or less ineffective\n in repression or upregulation of hARE-mediated gene expression.\n Interestingly, overexpression of Nrf1 and Nrf2 individually in Hep-G2\n and monkey kidney (COS1) cells significantly increased CAT gene\n expression from reporter plasmid hARE-thymidine kinase-CAT in\n transfected cells that were inducible by \u03b2-naphthoflavone and\n                    <jats:italic>tert<\/jats:italic>\n                    -butyl hydroquinone. These results indicated that\n hARE-mediated expression of the NQO\n                    <jats:sub>1<\/jats:sub>\n                    gene and its induction\n by xenobiotics and antioxidants are mediated by Nrf1 and Nrf2. The\n hARE-mediated basal expression, however, is repressed by overexpression\n of c-Fos and Fra1.\n                  <\/jats:p>","DOI":"10.1073\/pnas.93.25.14960","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:31:44Z","timestamp":1027679504000},"page":"14960-14965","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":915,"title":["Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase\n                    <sub>1<\/sub>\n                    \u2009gene"],"prefix":"10.1073","volume":"93","author":[{"given":"Radjendirane","family":"Venugopal","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Fox Chase Cancer Center, 7701 Burholme\r Avenue, Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anil\u2009K.","family":"Jaiswal","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Fox Chase Cancer Center, 7701 Burholme\r Avenue, Philadelphia, PA 19111"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1996,12,10]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(92)90694-E"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)42151-5"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.12.6894"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(94)90272-0"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)50219-8"},{"key":"e_1_3_2_6_2","first-page":"129","volume":"1072","author":"Angel P","year":"1991","unstructured":"P Angel, M Karim Biochim Biophys Acta 1072, 129\u2013157 (1991).","journal-title":"Biochim Biophys Acta"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.23.11371"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.21.9926"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.22.9000"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36651-6"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.270.19.11502"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1991.tb15691.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.83.16.5889"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.11.4972"},{"key":"e_1_3_2_15_2","first-page":"365","volume":"11","author":"De Cesare D","year":"1995","unstructured":"D De Cesare, D Vallone, A Caracciolo, P Sassone-Corsi, C Nerlov, P Verde Oncogene 11, 365\u2013376 (1995).","journal-title":"Oncogene"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ge.25.120191.001531"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/8.10.1549"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1994.tb20023.x"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.93.25.14960","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:41:38Z","timestamp":1649860898000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.93.25.14960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,12,10]]},"references-count":18,"journal-issue":{"issue":"25","published-print":{"date-parts":[[1996,12,10]]}},"alternative-id":["10.1073\/pnas.93.25.14960"],"URL":"https:\/\/doi.org\/10.1073\/pnas.93.25.14960","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1996,12,10]]},"assertion":[{"value":"1996-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-08-05","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1996-12-10","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}