{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T16:06:12Z","timestamp":1781107572794,"version":"3.54.1"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,6,6]]},"abstract":"<jats:p>\n                    Infectious proteins (prions) can arise\n                    <jats:italic>de novo<\/jats:italic>\n                    as well as by transmission from another individual.\n                    <jats:italic>De novo<\/jats:italic>\n                    prion generation is believed responsible for most cases of Creutzfeldt\u2013Jakob disease and for initiating the mad cow disease epidemic. However, the cellular components needed for prion generation have not been identified in any system. The [URE3] prion of\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    is an infectious form of Ure2p, apparently a self-propagating amyloid. We now demonstrate a protein required for\n                    <jats:italic>de novo<\/jats:italic>\n                    prion generation. Mks1p negatively regulates Ure2p and is itself negatively regulated by the presence of ammonia and by the Ras\u2013cAMP pathway. We find that in\n                    <jats:italic>mks1<\/jats:italic>\n                    \u0394 strains,\n                    <jats:italic>de novo<\/jats:italic>\n                    generation of the [URE3] prion is blocked, although [URE3] introduced from another strain is expressed and propagates stably. Ras2\n                    <jats:sup>Val19<\/jats:sup>\n                    increases cAMP production and also blocks [URE3] generation. These results emphasize the distinction between prion generation and propagation, and they show that cellular regulatory mechanisms can critically affect prion generation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.120168697","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:41:48Z","timestamp":1027680108000},"page":"6625-6629","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":33,"title":["A protein required for prion generation: [URE3] induction requires the Ras-regulated Mks1 protein"],"prefix":"10.1073","volume":"97","author":[{"given":"Herman K.","family":"Edskes","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Building 8, Room 225, 8 Center Drive, MSC 0830, Bethesda, MD 20892-0830"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reed B.","family":"Wickner","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Genetics, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Building 8, Room 225, 8 Center Drive, MSC 0830, Bethesda, MD 20892-0830"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2000,5,23]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.23.13363"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(96)10054-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.1.3"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.106.2.519-522.1971"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/yea.320040302"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.7909170"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.270.5233.93"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.23.12503"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00351802"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/144.4.1375"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.3109\/10409239709082674"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1996.tb00675.x"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5324.381"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.273.5275.622"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.13.6618"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80264-0"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.4.1498"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.283.5406.1339"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/jb.109.1.203-208.1972"},{"key":"e_1_3_2_20_2","first-page":"39","volume-title":"The Molecular Biology of the Yeast Saccharomyces: Metabolism and Gene Expression","author":"Cooper T G","year":"1982","unstructured":"T G Cooper The Molecular Biology of the Yeast Saccharomyces: Metabolism and Gene Expression, eds J N Strathern, E W Jones, J R Broach (Cold Spring Harbor Lab. 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