{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:52:37Z","timestamp":1760266357689},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2003,7,18]],"date-time":"2003-07-18T00:00:00Z","timestamp":1058486400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2003,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alterations in the rat tuberous sclerosis gene (<jats:italic>Tsc2<\/jats:italic>) cause renal cell carcinomas (RCCs) with complete penetrance. In this study, it was shown that the minimal core promoters of the rat <jats:italic>Tsc2<\/jats:italic> and endonuclease III 1 (<jats:italic>Nth1<\/jats:italic>) genes, lying in a 5\u2032\u2010to\u20105\u2032 arrangement, were localized in a 0.11\u2010kb region containing two Ets binding sites (EBSs). This region worked as a bidirectional promoter in a single reporter plasmid. Mutational inactivation of each of the two EBSs significantly reduced promoter activity. Moreover, gel shift assays revealed the presence of specific EBSs\u2010protein complexes. These results demonstrate that some members of the Ets family positively regulate the promoter activities of the <jats:italic>Tsc2<\/jats:italic>\/<jats:italic>Nth1<\/jats:italic> genes by binding to the EBSs. We identified Elf\u20101 as a binding factor for EBSs through super\u2010shift assays, and detected \u223c35 kDa bands with an EBSs\u2010containing DNA probe by Southwestern blot analysis. Forced expression of Elf\u20101 in cells, however, bidirectionally suppressed the activities of the <jats:italic>Tsc2<\/jats:italic>\/<jats:italic>Nth1<\/jats:italic> promoters. Elf\u20101 may be a negative regulator of <jats:italic>Tsc2<\/jats:italic>\/<jats:italic>Nth1<\/jats:italic> gene expression and may compete against positive regulators for binding to the EBSs. Our observations suggest that mechanisms that inactivate <jats:italic>Tsc2<\/jats:italic> gene expression, such as promoter suppression, may exist. \u00a9 2003 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mc.10123","type":"journal-article","created":{"date-parts":[[2003,7,22]],"date-time":"2003-07-22T10:12:10Z","timestamp":1058868730000},"page":"122-129","source":"Crossref","is-referenced-by-count":13,"title":["Ets protein Elf\u20101 bidirectionally suppresses transcriptional activities of the tumor suppressor <i>Tsc2<\/i> gene and the repair\u2010related <i>Nth1<\/i> gene"],"prefix":"10.1002","volume":"37","author":[{"given":"Satoshi","family":"Honda","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiyuki","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazunori","family":"Kajino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinji","family":"Urakami","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikio","family":"Igawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Okio","family":"Hino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2003,7,18]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5327.805"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90618-Z"},{"key":"e_1_2_7_4_2","first-page":"1201","article-title":"Tuberous sclerosis\u2010associated renal cell carcinoma. 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