{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:46:48Z","timestamp":1790711208046,"version":"4.1.0"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"8","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1995,4,11]]},"abstract":"<jats:p>Attachment of Ras protein to the membrane, which requires farnesylation at its C terminus, is essential for its biological activity. A promising pharmacological approach of antagonizing oncogenic Ras activity is to develop inhibitors of farnesyltransferase. We use Caenorhabditis elegans vulval differentiation, which is controlled by a Ras-mediated signal transduction pathway, as a model system to test previously identified farnesyltransferase inhibitors. We show here that two farnesyltransferase inhibitors, manumycin and gliotoxin, suppress the Multivulva phenotype resulting from an activated let-60 ras mutation, but not the Multivulva phenotype resulting from mutations in the lin-1 gene or the lin-15 gene, which act downstream and upstream of let-60 ras, respectively, in the signaling pathway. These results are consistent with the idea that the suppression of the Multivulva phenotype of let-60 ras by the two inhibitors is specific for Ras protein and that the mutant Ras protein might be more sensitive than wild-type Ras to the farnesyltransferase inhibitors. This work suggests that C. elegans vulval development could be a simple and effective in vivo system for evaluation of farnesyltransferase inhibitors against Ras-activated tumors.<\/jats:p>","DOI":"10.1073\/pnas.92.8.3333","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:31:03Z","timestamp":1149067863000},"page":"3333-3337","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":82,"title":["Ras farnesyltransferase inhibitors suppress the phenotype resulting from an activated ras mutation in Caenorhabditis elegans."],"prefix":"10.1073","volume":"92","author":[{"given":"M","family":"Hara","sequence":"first","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder 80309-0347, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder 80309-0347, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1995,4,11]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.92.8.3333","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:07:17Z","timestamp":1649858837000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.92.8.3333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,4,11]]},"references-count":0,"journal-issue":{"issue":"8","published-print":{"date-parts":[[1995,4,11]]}},"alternative-id":["10.1073\/pnas.92.8.3333"],"URL":"https:\/\/doi.org\/10.1073\/pnas.92.8.3333","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,4,11]]},"assertion":[{"value":"1995-04-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}