{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:33:51Z","timestamp":1787063631593,"version":"build-2736575974"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5205,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2001,6]]},"abstract":"\n \n \n The multidrug resistance protein\n Mdr1b<\/jats:italic>\n in rats is up\u2013regulated during liver regeneration after partial hepatectomy or after endotoxin treatment. We hypothesize that up\u2013regulation of\n Mdr1b<\/jats:italic>\n in these models is TNF\u2013\u03b1-dependent. The mechanism of\n Mdr1b<\/jats:italic>\n activation by TNF\u2013\u03b1 is unknown as TNF\u2013\u03b1 can signal through various pathways, including NF\u2013\u03baB and p53, transcription factors for which binding sites in the\n Mdr1b<\/jats:italic>\n promoter have been identified. We aimed to elucidate the mechanism of up\u2013regulation of\n Mdr1b<\/jats:italic>\n by TNF\u2013\u03b1. We selectively used constructs expressing dominant negative Fas\u2013associated death domain protein (FADD), TNF receptor associated factor\u20132 (TRAF2) or I\u03baB to inhibit pathways downstream of the TNF receptor. Further, the proteasome inhibitor MG\u2013132 was used, which prevents the breakdown of I\u03baB. We show a critical role for NF\u2013\u03baB in activation of\n Mdr1b<\/jats:italic>\n gene expression both in primary rat hepatocytes and in rat hepatoma H\u20134\u2013II\u2013E cells. Because p53 is up\u2013regulated by TNF\u2013\u03b1 in an NF\u2013\u03baB-dependent manner and the\n Mdr1b<\/jats:italic>\n promoter contains a p53 binding site, we used liver cells expressing a dominant negative p53 to show that TNF\u2013\u03b1 up\u2013regulation of\n Mdr1b<\/jats:italic>\n is independent of functional p53. Using transient transfection assays, we show that\n Mdr1b<\/jats:italic>\n up\u2013regulation correlates with activation of the promoter. Mutation of the NF\u2013\u03baB site in the\n Mdr1b<\/jats:italic>\n promoter prevents its induction by TNF\u2013\u03b1. In conclusion our results show that activation of the rat\n Mdr1b<\/jats:italic>\n gene by TNF\u2013\u03b1 is a result of NF\u2013\u03baB signaling and independent of p53. (Hepatology 2001;33:1425\u20131431.)\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1053\/jhep.2001.24667","type":"journal-article","created":{"date-parts":[[2002,8,24]],"date-time":"2002-08-24T23:46:10Z","timestamp":1030232770000},"page":"1425-1431","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":56,"title":["Induction Of Mdr1b Expression by Tumor Necrosis Factor\u2013\u03b1 in Rat Liver Cells Is Independent of P53 But Requires Nf\u2013\u03baB Signaling"],"prefix":"10.1097","volume":"33","author":[{"given":"Jenny E.","family":"Ros","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Schuetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariska","family":"Geuken","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad","family":"Streetz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Moshage","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folkert","family":"Kuipers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Manns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.M.","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Trautwein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","container-title":["Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1053%2Fjhep.2001.24667","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.lww.com\/01515467-200106000-00012","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T06:27:15Z","timestamp":1733034435000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.lww.com\/01515467-200106000-00012"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,6]]},"references-count":0,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2001]]}},"URL":"https:\/\/doi.org\/10.1053\/jhep.2001.24667","relation":{},"ISSN":["0270-9139"],"issn-type":[{"value":"0270-9139","type":"print"}],"subject":[],"published":{"date-parts":[[2001,6]]}}}