Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
1993-8-30
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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
25
pubmed:volume
268
pubmed:geneSymbol
c-fos, cad, egr-2, rep-3b, v-raf
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15674-80
pubmed:dateRevised
2009-11-19
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
pubmed:year
1993
pubmed:articleTitle
An inhibitory Raf-1 mutant suppresses expression of a subset of v-raf-activated genes.
pubmed:affiliation
McArdle Laboratory for Cancer Research, University of Wisconsin-Madison 53706.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.