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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
21
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pubmed:dateCreated |
1993-8-30
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pubmed:abstractText |
The proto-oncogene Raf-1 is a cytoplasmic serine/threonine kinase implicated in the signaling process in cell proliferation. To determine if Raf-1 is sufficient and necessary to transmit mitogenic signals to growth-responsive genes, we examined the effect of constitutively activated (v-raf) or inhibitory (Raf-C4) Raf-1 proteins on reporter gene activation in transient expression assays of NIH 3T3 cells. In serum-starved cells, v-raf strongly activated transcription from the promoters of the immediate-early genes c-fos and egr-2, as well as the proximal or B promoter of the late growth response gene rep-3 (rep-3b). Two other late response gene promoters, cad and dhfr, were only modestly activated by v-raf, however. An individual serum response element from the c-fos or egr-2 promoter conferred both serum-inducibility and v-raf-responsiveness to a heterologous promoter. Consistent with the degree to which antisense c-raf-1 RNA and dominant-negative Raf-1 proteins interfere with NIH 3T3 cell proliferation, Raf-C4 reduced serum-induced transcription from the egr-2 and rep-3b promoters in a dose-dependent manner by 50%. In contrast, Raf-C4 did not significantly reduce transcription from the c-fos or cad promoters or the serum response element-driven heterologous promoters. We conclude that Raf-1 is both sufficient and necessary to activate a subset of early and late growth response genes.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Oligodeoxyribonucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Oncogene Proteins v-raf,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf,
http://linkedlifedata.com/resource/pubmed/chemical/Retroviridae Proteins, Oncogenic
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
268
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pubmed:geneSymbol |
c-fos,
cad,
egr-2,
rep-3b,
v-raf
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
15674-80
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:8340392-3T3 Cells,
pubmed-meshheading:8340392-Animals,
pubmed-meshheading:8340392-Base Sequence,
pubmed-meshheading:8340392-Blood,
pubmed-meshheading:8340392-Gene Expression Regulation,
pubmed-meshheading:8340392-Mice,
pubmed-meshheading:8340392-Molecular Sequence Data,
pubmed-meshheading:8340392-Mutation,
pubmed-meshheading:8340392-Oligodeoxyribonucleotides,
pubmed-meshheading:8340392-Oncogene Proteins v-raf,
pubmed-meshheading:8340392-Promoter Regions, Genetic,
pubmed-meshheading:8340392-Protein-Tyrosine Kinases,
pubmed-meshheading:8340392-Proto-Oncogene Proteins,
pubmed-meshheading:8340392-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:8340392-Retroviridae Proteins, Oncogenic,
pubmed-meshheading:8340392-Signal Transduction,
pubmed-meshheading:8340392-Transcription, Genetic,
pubmed-meshheading:8340392-Transcriptional Activation
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pubmed:year |
1993
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pubmed:articleTitle |
An inhibitory Raf-1 mutant suppresses expression of a subset of v-raf-activated genes.
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pubmed:affiliation |
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison 53706.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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