{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T07:15:31Z","timestamp":1791357331062,"version":"4.3.1"},"reference-count":61,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2005,1,1]],"date-time":"2005-01-01T00:00:00Z","timestamp":1104537600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2005,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Cryptococcus neoformans<\/jats:italic>is an opportunistic human fungal pathogen that elaborates several virulence attributes, including a polysaccharide capsule and melanin pigments. A conserved G\u03b1 protein\/cyclic AMP (cAMP) pathway controls melanin and capsule production. To identify targets of this pathway, we used an expression profiling approach to define genes that are transcriptionally regulated by the G\u03b1 protein Gpa1. This approach revealed that Gpa1 transcriptionally regulates multiple genes involved in capsule assembly and identified two additional genes with a marked dependence on Gpa1 for transcription. The first is the<jats:italic>LAC1<\/jats:italic>gene, encoding the laccase enzyme that catalyzes a rate-limiting step in diphenol oxidation and melanin production. The second gene identified (<jats:italic>LAC2<\/jats:italic>) is adjacent to the<jats:italic>LAC1<\/jats:italic>gene and encodes a second laccase that shares 75% nucleotide identity with<jats:italic>LAC1<\/jats:italic>. Similar to the<jats:italic>LAC1<\/jats:italic>gene,<jats:italic>LAC2<\/jats:italic>is induced in response to glucose deprivation. However,<jats:italic>LAC2<\/jats:italic>basal transcript levels are much lower than those for<jats:italic>LAC1<\/jats:italic>. Accordingly, a<jats:italic>lac2<\/jats:italic>mutation results in only a modest delay in melanin formation.<jats:italic>LAC2<\/jats:italic>overexpression suppresses the melanin defects of<jats:italic>gpa1<\/jats:italic>and<jats:italic>lac1<\/jats:italic>mutants and partially restores virulence of these strains. These studies provide mechanistic insights into the regulation of capsule and melanin production by the<jats:italic>C. neoformans<\/jats:italic>cAMP pathway and demonstrate that multiple laccases contribute to<jats:italic>C. neoformans<\/jats:italic>melanin production and pathogenesis.<\/jats:p>","DOI":"10.1128\/ec.4.1.190-201.2005","type":"journal-article","created":{"date-parts":[[2005,1,11]],"date-time":"2005-01-11T01:16:15Z","timestamp":1105406175000},"page":"190-201","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":160,"title":["Transcriptional Network of Multiple Capsule and Melanin Genes Governed by the<i>Cryptococcus neoformans<\/i>Cyclic AMP Cascade"],"prefix":"10.1128","volume":"4","author":[{"given":"Read","family":"Pukkila-Worley","sequence":"first","affiliation":[{"name":"Departments of Medicine"},{"name":"Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quincy D.","family":"Gerrald","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Kraus","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Molecular Genetics and Microbiology"},{"name":"Pharmacology and Cancer Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jose\u0301e","family":"Boily","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Molecular Genetics and Microbiology"},{"name":"Pharmacology and Cancer Biology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Davis","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven S.","family":"Giles","sequence":"additional","affiliation":[{"name":"Departments of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary M.","family":"Cox","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Heitman","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Molecular Genetics and Microbiology"},{"name":"Pharmacology and Cancer Biology"},{"name":"Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Andrew","family":"Alspaugh","sequence":"additional","affiliation":[{"name":"Departments of Medicine"},{"name":"Molecular Genetics and Microbiology"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.7.2291-2296.1991"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.11.23.3206"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.1.75-84.2002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-230X(08)60809-X"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/mcb.14.7.4912-4919.1994"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.5.2230-2236.1998"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.18.5636-5643.1999"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.64.6.1977-1983.1996"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.2.443-448.2000"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1080\/02681219580000521"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-8-2607"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2000.02213.x"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2003.03563.x"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5338.680"},{"key":"e_1_3_2_16_2","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1111\/j.1439-0507.1992.tb00814.x","volume":"35","year":"1992","unstructured":"Dixon, D. M., J. Migliozzi, C. R. Cooper, O. Solis, B. G. Breslin, and P. J. Szaniszlo. 1992. Melanized and nonmelanized multicellular-form mutants of Wangiella dermatitidis in mice: mortality and histopathology studies. Mycoses35:17-21.","journal-title":"Mycoses"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/JB.181.17.5482-5488.1999"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.21.9.3179-3191.2001"},{"key":"e_1_3_2_19_2","first-page":"539","volume":"252","year":"1996","unstructured":"Fernandez-Larrea, J., and U. Stahl. 1996. Isolation and characterization of a laccase gene from Podospora anserina. Mol. Gen. Genet.252:539-551.","journal-title":"Mol. Gen. Genet."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI112000"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.1.14-26.2004"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00294-003-0452-x"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2001.02651.x"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.5.1249-1260.2004"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/bit.10681"},{"key":"e_1_3_2_26_2","unstructured":"Kwon-Chung K. J. and J. E. Bennett. 1992. Cryptococcosis p. 397-446. In Medical Mycology. Lea & Febiger Malvern Pa."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.150.3.1414-1421.1982"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.51.1.218-223.1986"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1087-1845(02)00526-1"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.69.10.6257-6263.2003"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-4028(200107)41:3\/4<185::AID-JOBM185>3.0.CO;2-T"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1080\/mmy.39.1.151.154"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1006\/fgbi.1997.1017"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.3.6.1513-1524.2004"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.03059.x"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.232568599"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-05-0370"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02356-4"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.1.745"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.10.5.724-729.1979"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2001.tb10741.x"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.19.7.4874"},{"key":"e_1_3_2_43_2","first-page":"177","volume":"101","year":"1980","unstructured":"Perfect, J. R., S. D. Lang, and D. T. Durack. 1980. Chronic cryptococcal meningitis: a new experimental model in rabbits. Am. J. Pathol.101:177-194.","journal-title":"Am. J. Pathol."},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-139-1-171"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1099\/13500872-142-6-1557"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13783"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.184.2.377"},{"key":"e_1_3_2_48_2","unstructured":"Sambrook J. E. F. Fritsch and T. Maniatis. 1989. Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory Press Cold Spring Harbor N.Y."},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.02801.x"},{"key":"e_1_3_2_50_2","first-page":"3","year":"1991","unstructured":"Sherman, F. 1991. Getting started with yeast, p. 3-21. In C. Guthrie and G. R. Fink (ed.), Methods in enzymology, vol. 194. Academic Press, Inc., San Diego, Calif..","journal-title":"Methods in enzymology, vol. 194"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.261418798"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2001.tb09475.x"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.175.5.1405-1411.1993"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.7.2849-2856.1994"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2002-3-7-research0034"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/167.1.186"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.1.352-362.2000"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1128\/aem.60.10.3864-3866.1994"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-148-1-191"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.176.3.656-664.1994"},{"key":"e_1_3_2_61_2","first-page":"e99\u2014e107","volume":"2","year":"1997","unstructured":"Williamson, P. R. 1997. Laccase and melanin in the pathogenesis of Cryptococcus neoformans. Front. Biosci.2:e99\u2014e107.","journal-title":"Front. Biosci."},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.71.11.6155-6164.2003"}],"container-title":["Eukaryotic Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/EC.4.1.190-201.2005","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/EC.4.1.190-201.2005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T18:32:52Z","timestamp":1705689172000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/EC.4.1.190-201.2005"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,1]]},"references-count":61,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2005,1]]}},"alternative-id":["10.1128\/EC.4.1.190-201.2005"],"URL":"https:\/\/doi.org\/10.1128\/ec.4.1.190-201.2005","relation":{},"ISSN":["1535-9778","1535-9786"],"issn-type":[{"value":"1535-9778","type":"print"},{"value":"1535-9786","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,1]]},"assertion":[{"value":"2004-10-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-10-13","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}