{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T12:56:21Z","timestamp":1765976181329,"version":"build-2065373602"},"reference-count":49,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[1999,10,1]],"date-time":"1999-10-01T00:00:00Z","timestamp":938736000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1\u2010CA80900"],"award-info":[{"award-number":["RO1\u2010CA80900"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council Canada","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[1999,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The human multidrug resistance P\u2010glycoprotein (P\u2010gp) contributes to the phenomenon of multidrug resistance during cancer and AIDS chemotherapy. A potential novel strategy to circumvent the effects of P\u2010gp during chemotherapy is to prevent maturation of P\u2010gp during biosynthesis so that the transporter does not reach the cell surface. Here we report that immature, core\u2010glycosylated P\u2010gp that is prevented from reaching the cell surface by processing mutations or by proteasome inhibitors such as lactacystin or MG\u2010132 exhibited no detectable drug\u2010stimulated ATPase activity. Disulfide cross\u2010linking analysis also showed that the immature P\u2010gp did not exhibit ATP\u2010induced conformational changes as found in the mature enzyme. In addition, the immature P\u2010gp was more sensitive to trypsin than the mature enzyme. These results suggest that P\u2010gp is unlikely to be functional immediately after synthesis. These differences in the structural and enzymatic properties of the mature and core\u2010glycosylated, immature P\u2010gp could potentially be used during chemotherapy, and should result in the search for compounds that can specifically inhibit the maturation of P\u2010gp.\u2014Loo, T. W., Clarke, D. M. The human multi\u2010drug resistance P\u2010glycoprotein is inactive when its maturation is inhibited: potential for a role in cancer chemotherapy.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 13, 1724\u20131732 (1999)\n                  <\/jats:p>","DOI":"10.1096\/fasebj.13.13.1724","type":"journal-article","created":{"date-parts":[[2018,1,25]],"date-time":"2018-01-25T04:42:55Z","timestamp":1516855375000},"page":"1724-1732","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["The human multidrug resistance P\u2010glycoprotein is inactive when its maturation is inhibited: potential for a role in cancer chemotherapy"],"prefix":"10.1096","volume":"13","author":[{"given":"Tip W.","family":"Loo","sequence":"first","affiliation":[{"name":"MRC Group in Membrane Biology Department of Medicine Department of Biochemistry University of Toronto  Toronto Ontario M5S 1A8 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M.","family":"Clarke","sequence":"additional","affiliation":[{"name":"MRC Group in Membrane Biology Department of Medicine Department of Biochemistry University of Toronto  Toronto Ontario M5S 1A8 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[1999,10]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0959-8049(96)00069-X"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(76)90160-7"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(85)90082-8"},{"key":"e_1_2_7_5_1","first-page":"1174","article-title":"Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross\u2010resistance, radioautographic, and cytogenetic studies","volume":"30","author":"Biedler J. 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