{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:32:16Z","timestamp":1781109136357,"version":"3.54.1"},"reference-count":25,"publisher":"National Academy of Sciences","issue":"42","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,10,17]]},"abstract":"<jats:p>\n                    Hemiasterlin is a potent antimitotic peptide that interferes with microtubule dynamics at picomolar concentrations in cell culture. The molecule largely eludes P glycoprotein-mediated drug efflux, and an analog is currently being evaluated in clinical trials as cancer chemotherapy. From a nonclonal genetic screen in\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    we isolated eight independent mutants resistant to a synthetic hemiasterlin analog. In one recessive mutant,\n                    <jats:italic>phb-2(ad2154)<\/jats:italic>\n                    , a point mutation in prohibitin 2 (E130K) protects worms from drug-induced injury. Data indicate that direct binding of hemiasterlin to prohibitin 2 is unlikely. In fact,\n                    <jats:italic>C. elegans<\/jats:italic>\n                    <jats:italic>phb-2(ad2154)<\/jats:italic>\n                    was also found to be resistant to numerous other drugs that bind tubulin and to camptothecin, yet this mutant was sensitive to nocodazole and phalloidin. Thus, prohibitin 2 is implicated in a previously uncharacterized pathway of multidrug resistance.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0607338103","type":"journal-article","created":{"date-parts":[[2006,10,10]],"date-time":"2006-10-10T22:54:28Z","timestamp":1160520868000},"page":"15523-15528","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":16,"title":["A missense mutation in\n                    <i>Caenorhabditis elegans<\/i>\n                    prohibitin 2 confers an atypical multidrug resistance"],"prefix":"10.1073","volume":"103","author":[{"given":"Iryna","family":"Zubovych","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Doundoulakis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick G.","family":"Harran","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael G.","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9038"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2006,10,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00726-002-0349-x"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050564"},{"key":"e_1_3_3_3_2","first-page":"1838","volume":"63","author":"Loganzo F","year":"2003","unstructured":"F Loganzo, CM Discafani, T Annable, C Beyer, S Musto, M Hari, X Tan, C Hardy, R Hernandez, M Baxter, et al. Cancer Res 63, 1838\u20131845 (2003).","journal-title":"Cancer Res"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi049300"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2005.030.03.886482"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(99)00089-9"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/np020375t"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M304877200"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/19.11.2444"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-09-0807"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M305171200"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(94)01444-6"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06689.x"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3835(94)90320-4"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1615-9861(200206)2:6<706::AID-PROT706>3.0.CO;2-E"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v10.i15.2179"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5492.809"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-313X.2005.02505.x"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.5.1989-1999.2005"},{"key":"e_1_3_3_20_2","volume-title":"Methods, the Nematode Caenorhabditis elegans","author":"Sulston JE","year":"1988","unstructured":"JE Sulston, JA Hodgkin Methods, the Nematode Caenorhabditis elegans (Cold Spring Harbor Lab Press, Cold Spring Harbor, NY, 1988)."},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/133.4.897"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(69)90288-5"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.76.3.1333"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/77.1.71"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-679X(08)61399-0"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0607338103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:54:50Z","timestamp":1649778890000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0607338103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,10,17]]},"references-count":25,"journal-issue":{"issue":"42","published-print":{"date-parts":[[2006,10,17]]}},"alternative-id":["10.1073\/pnas.0607338103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0607338103","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,10,17]]},"assertion":[{"value":"2006-07-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-10-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}