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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
11
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pubmed:dateCreated |
1993-5-6
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pubmed:abstractText |
The ras oncogene product, Ras, is synthesized in vivo as a precursor protein that requires post-translational processing to become biologically active and to be capable of transforming mammalian cells. Farnesylation appears to be a critical modification of Ras, and thus inhibitors of the farnesyl-protein transferase (FPTase) that catalyzes this reaction may block ras-dependent tumorigenesis. Three structural classes of FPTase inhibitors were identified: (alpha-hydroxyfarnesyl)phosphonic acid, chaetomellic acids, and zaragozic acids. By comparison, these compounds were weaker inhibitors of geranylgeranyl-protein transferases. Each of these inhibitors was competitive with respect to farnesyl diphosphate in the FPTase reaction. All compounds were assayed for inhibition of Ras processing in Ha-ras-transformed NIH3T3 fibroblasts. Ras processing was inhibited by 1 microM (alpha-hydroxyfarnesyl)phosphonic acid. Neither chaetomellic acid nor zaragozic acid were active in this assay. These results are the first demonstration that a small organic chemical selected for inhibition of FPTase can inhibit Ras processing in vivo.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Alkyl and Aryl Transferases,
http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Bicyclo Compounds, Heterocyclic,
http://linkedlifedata.com/resource/pubmed/chemical/Farnesol,
http://linkedlifedata.com/resource/pubmed/chemical/Maleates,
http://linkedlifedata.com/resource/pubmed/chemical/Organophosphorus Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Transferases,
http://linkedlifedata.com/resource/pubmed/chemical/Tricarboxylic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/geranylgeranyltransferase type-I,
http://linkedlifedata.com/resource/pubmed/chemical/p21(ras) farnesyl-protein...,
http://linkedlifedata.com/resource/pubmed/chemical/squalestatin 1
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
268
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7617-20
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:8463291-3T3 Cells,
pubmed-meshheading:8463291-Alkyl and Aryl Transferases,
pubmed-meshheading:8463291-Animals,
pubmed-meshheading:8463291-Bicyclo Compounds,
pubmed-meshheading:8463291-Bicyclo Compounds, Heterocyclic,
pubmed-meshheading:8463291-Brain,
pubmed-meshheading:8463291-Cattle,
pubmed-meshheading:8463291-Cell Line, Transformed,
pubmed-meshheading:8463291-Farnesol,
pubmed-meshheading:8463291-Gene Expression Regulation,
pubmed-meshheading:8463291-Genes, ras,
pubmed-meshheading:8463291-Kinetics,
pubmed-meshheading:8463291-Maleates,
pubmed-meshheading:8463291-Mice,
pubmed-meshheading:8463291-Organophosphorus Compounds,
pubmed-meshheading:8463291-Phosphonic Acids,
pubmed-meshheading:8463291-Protein Processing, Post-Translational,
pubmed-meshheading:8463291-Transferases,
pubmed-meshheading:8463291-Tricarboxylic Acids
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pubmed:year |
1993
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pubmed:articleTitle |
Selective inhibition of farnesyl-protein transferase blocks ras processing in vivo.
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pubmed:affiliation |
Department of Cancer Research, Merck Research Laboratories, West Point, Pennsylvania 19486.
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pubmed:publicationType |
Journal Article
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