{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T04:31:07Z","timestamp":1793334667131,"version":"4.5.0"},"reference-count":98,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2011,8,23]],"date-time":"2011-08-23T00:00:00Z","timestamp":1314057600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:italic>Cryptococcus neoformans<\/jats:italic>is a human fungal pathogen that is the causative agent of cryptococcosis and fatal meningitis in immuno\u2010compromised hosts. Recent studies suggest that copper (Cu) acquisition plays an important role in<jats:italic>C.\u2003neoformans<\/jats:italic>virulence, as mutants that lack Cuf1, which activates the Ctr4 high affinity Cu importer, are hypo\u2010virulent in mouse models. To understand the constellation of Cu\u2010responsive genes in<jats:italic>C.\u2003neoformans<\/jats:italic>and how their expression might contribute to virulence, we determined the transcript profile of<jats:italic>C.\u2003neoformans<\/jats:italic>in response to elevated Cu or Cu deficiency. We identified two metallothionein genes (<jats:italic>CMT1<\/jats:italic>and<jats:italic>CMT2<\/jats:italic>), encoding cysteine\u2010rich Cu binding and detoxifying proteins, whose expression is dramatically elevated in response to excess Cu. We identified a new<jats:italic>C.\u2003neoformans<\/jats:italic>Cu transporter, CnCtr1, that is induced by Cu deficiency and is distinct from CnCtr4 and which shows significant phylogenetic relationship to Ctr1 from other fungi. Surprisingly, in contrast to other fungi, we found that induction of both Cn<jats:italic>CTR1<\/jats:italic>and Cn<jats:italic>CTR4<\/jats:italic>expression under Cu limitation, and<jats:italic>CMT1<\/jats:italic>and<jats:italic>CMT2<\/jats:italic>in response to Cu excess, are dependent on the CnCuf1 Cu metalloregulatory transcription factor. These studies set the stage for the evaluation of the specific Cuf1 target genes required for virulence in<jats:italic>C.\u2003neoformans<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/j.1365-2958.2011.07794.x","type":"journal-article","created":{"date-parts":[[2011,8,8]],"date-time":"2011-08-08T09:20:30Z","timestamp":1312795230000},"page":"1560-1576","source":"Crossref","is-referenced-by-count":100,"title":["The copper regulon of the human fungal pathogen<i>Cryptococcus neoformans<\/i>H99"],"prefix":"10.1111","volume":"81","author":[{"given":"Chen","family":"Ding","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edgar Mauricio Medina","family":"Tovar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Fitzpatrick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Desmond G.","family":"Higgins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis J.","family":"Thiele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,8,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.115.3.734"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000217"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.05.001"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M011256200"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300861200"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.28392-0"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.046854-0"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.9.4091"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.11.3332"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-1119(84)90235-X"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/S0026-895X(25)10183-1","article-title":"Regulation of metallothionein gene expression in mammalian cells by gold compounds","volume":"29","author":"Butt T.R.","year":"1986","journal-title":"Mol Pharmacol"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/597306"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000850"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016936"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/9781555818241"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.14.7.4912"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.7.2.146-152.1978"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00058-10"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0012503"},{"key":"e_1_2_6_22_1","doi-asserted-by":"crossref","first-page":"25295","DOI":"10.1016\/S0021-9258(18)47246-8","article-title":"CRS5 encodes a metallothionein\u2010like protein in Saccharomyces cerevisiae","volume":"269","author":"Culotta V.C.","year":"1994","journal-title":"J Biol Chem"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-8-2607"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.16.11645"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2006.00504.x"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.3109\/00365548809032452"},{"key":"e_1_2_6_27_1","doi-asserted-by":"crossref","first-page":"16895","DOI":"10.1016\/S0021-9258(19)75973-0","article-title":"Yeast metallothionein function in metal ion detoxification","volume":"261","author":"Ecker D.J.","year":"1986","journal-title":"J Biol Chem"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6941.2006.00060.x"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg012"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04220"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(88)90229-2"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.5.3124-3127.2005"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/10635150390235520"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3887570"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110555"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.05427-0"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.11.1546"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1128\/CDLI.7.1.125-128.2000"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.37.23805"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00261675"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2009.01619.x"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1567-1364.2011.00733.x"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10059-011-0011-0"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040410"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0040045"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00166-09"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb06198.x"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02917243"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)01164-9"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2148-6-29"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01963468"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.72"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.15.1917"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.25.15951"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.51.36252"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.0020187"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.3109\/10715769609149059"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.11.6034-6039.1999"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05299.x"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1103773"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812808106"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1128\/JB.01357-06"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1001322"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.3.1693-1699.2004"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-145-9-2423"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.18.5.2514"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M005392200"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00775-009-0591-8"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1367-5931(02)00298-3"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202547200"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.288.5468.1062"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703397200"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411669200"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00350-08"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.2.377"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1301805"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00277-06"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.2202\/1544-6115.1027"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M609766200"},{"key":"e_1_2_6_80_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.9.2.421"},{"key":"e_1_2_6_81_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.8.7.2745"},{"key":"e_1_2_6_82_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3080806"},{"key":"e_1_2_6_83_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.5.1405-1411.1993"},{"key":"e_1_2_6_84_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.091062498"},{"key":"e_1_2_6_85_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2005.04779.x"},{"key":"e_1_2_6_86_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04474.x"},{"key":"e_1_2_6_87_1","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.3.656-664.1994"},{"key":"e_1_2_6_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)38592-7"},{"key":"e_1_2_6_89_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.28.17711"},{"key":"e_1_2_6_90_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-11-50"},{"key":"e_1_2_6_91_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2229-11-69"},{"key":"e_1_2_6_92_1","first-page":"11191","article-title":"NMR study of the exchange coupling in the trinuclear cluster of the multicopper oxidase Fet3p","volume":"132","author":"Zaballa M.E.","year":"2010","journal-title":"BMC Plant Biol"},{"key":"e_1_2_6_93_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M102004200"},{"key":"e_1_2_6_94_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M309820200"},{"key":"e_1_2_6_95_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03752.x"},{"key":"e_1_2_6_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.femsyr.2004.04.004"},{"key":"e_1_2_6_97_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.3.1277"},{"key":"e_1_2_6_98_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.9.5589-5596.2001"},{"key":"e_1_2_6_99_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03340.x"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2958.2011.07794.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2958.2011.07794.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T10:56:02Z","timestamp":1741431362000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2958.2011.07794.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,8,23]]},"references-count":98,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2011,9]]}},"alternative-id":["10.1111\/j.1365-2958.2011.07794.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2958.2011.07794.x","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,8,23]]}}}