{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T08:06:58Z","timestamp":1791965218682,"version":"4.3.4"},"reference-count":53,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2012,7,5]],"date-time":"2012-07-05T00:00:00Z","timestamp":1341446400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes to Cells"],"published-print":{"date-parts":[[2012,8]]},"abstract":"<jats:p>The target of rapamycin (<jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content>) protein kinase plays central roles in the regulation of cell growth in response to nutritional availability. <jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> forms two distinct multiprotein complexes termed <jats:styled-content style=\"fixed-case\">TOR<\/jats:styled-content> complex 1 (<jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1) and <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>2. Typically, only the activity of <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 is inhibited by the immunosuppressant rapamycin. Although rapamycin strongly inhibits cell growth of the budding yeast <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>accharomyces cerevisiae<\/jats:italic> through inhibition of <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1, growth of the fission yeast <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>chizosaccharomyces pombe<\/jats:italic> appears to be resistant to rapamycin. Here, we demonstrate that rapamycin inhibits the kinase activity of <jats:italic>S.\u00a0pombe <\/jats:italic><jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 <jats:italic>in vitro<\/jats:italic> in a similar manner to <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 of other organisms. We furthermore show that incomplete inhibition of <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 by rapamycin underlies the apparent rapamycin resistance of <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>.\u00a0pombe<\/jats:italic>. In the presence of caffeine, which potentially lowers <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 activity, the growth of wild\u2010type <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>.\u00a0pombe<\/jats:italic> cells is sensitive to rapamycin in a <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1\u2010dependent manner. Moreover, treatment of <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>.\u00a0pombe<\/jats:italic> cells with rapamycin plus caffeine induces starvation\u2010specific gene expression and autophagy, similarly to cells with reduced <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 activity. These results indicate that rapamycin does inhibit <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 in <jats:italic><jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>.\u00a0pombe<\/jats:italic>, but the inhibition is not sufficient to cause a growth defect. These findings establish a universal action of rapamycin on <jats:styled-content style=\"fixed-case\">TORC<\/jats:styled-content>1 inhibition.<\/jats:p>","DOI":"10.1111\/j.1365-2443.2012.01618.x","type":"journal-article","created":{"date-parts":[[2012,7,5]],"date-time":"2012-07-05T14:09:43Z","timestamp":1341497383000},"page":"698-708","source":"Crossref","is-referenced-by-count":53,"title":["TORC1 of fission yeast is rapamycin\u2010sensitive"],"prefix":"10.1111","volume":"17","author":[{"given":"Terunao","family":"Takahara","sequence":"first","affiliation":[{"name":"Institute of Molecular and Cellular Biosciences The University of Tokyo 1\u20101\u20101 Yayoi Bunkyo\u2010ku Tokyo 113\u20100032 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuya","family":"Maeda","sequence":"additional","affiliation":[{"name":"Institute of Molecular and Cellular Biosciences The University of Tokyo 1\u20101\u20101 Yayoi Bunkyo\u2010ku Tokyo 113\u20100032 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,7,5]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.03241"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600384"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90645.2008"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.13.10.6012"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.11.4947"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0809136105"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000038"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20090489"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2122003re15"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2007.01141.x"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1715094"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.5.1.105"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002940050456"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.7.3.5245"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1183"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01344-09"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002940100198"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00808-5"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2007.01041.x"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00636-6"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2672"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng951"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01039-06"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.12.037"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00294-006-0067-0"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.060319"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.7.3963"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M801546200"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.22.6485"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1356-9597.2004.00727.x"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/10409230802254911"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1646"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M603107200"},{"key":"e_1_2_6_35_1","first-page":"4375","article-title":"Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine","volume":"59","author":"Sarkaria J.N.","year":"1999","journal-title":"Cancer Res."},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00326301"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809207200"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01879-08"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M700857200"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.096222"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb900193e"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900301200"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608510104"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2007.04.020"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2006.01025.x"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M010446200"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.179.20.6325-6334.1997"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102090200"},{"key":"e_1_2_6_49_1","first-page":"251","volume-title":"The enzymes, Vol. 27 (Structure, function and regulation of TOR complexes from yeasts to mammals)","author":"Weisman R.","year":"2010"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.104.034983"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.106.064170"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.016"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M505553200"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7601239"}],"container-title":["Genes to Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2443.2012.01618.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2443.2012.01618.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,30]],"date-time":"2023-10-30T05:13:42Z","timestamp":1698642822000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2443.2012.01618.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,7,5]]},"references-count":53,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2012,8]]}},"alternative-id":["10.1111\/j.1365-2443.2012.01618.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2443.2012.01618.x","archive":["Portico"],"relation":{},"ISSN":["1356-9597","1365-2443"],"issn-type":[{"value":"1356-9597","type":"print"},{"value":"1365-2443","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,7,5]]}}}