@prefix dcterms: .
@prefix this: .
@prefix sub: .
@prefix beldoc: .
@prefix rdfs: .
@prefix rdf: .
@prefix xsd: .
@prefix dce: .
@prefix pav: .
@prefix np: .
@prefix belv: .
@prefix prov: .
@prefix go: .
@prefix Protein: .
@prefix entrez: .
@prefix geneProductOf: .
@prefix hasAgent: .
@prefix species: .
@prefix occursIn: .
@prefix pubmed: .
@prefix orcid: .
sub:Head {
this: np:hasAssertion sub:assertion;
np:hasProvenance sub:provenance;
np:hasPublicationInfo sub:pubinfo;
a np:Nanopublication .
}
sub:assertion {
sub:_1 hasAgent: sub:_2;
a go:0003824 .
sub:_2 geneProductOf: entrez:81638;
a Protein: .
sub:_3 occursIn: species:10116;
rdf:object go:0008283;
rdf:predicate belv:increases;
rdf:subject sub:_1;
a rdf:Statement .
sub:assertion rdfs:label "cat(p(EGID:81638)) -> bp(GO:\"cell proliferation\")" .
}
sub:provenance {
beldoc: dce:description "Approximately 61,000 statements.";
dce:rights "Copyright (c) 2011-2012, Selventa. All rights reserved.";
dce:title "BEL Framework Large Corpus Document";
pav:authoredBy sub:_5;
pav:version "1.4" .
sub:_4 prov:value "Cyclin D1 protein expression is regulated by mitogenic stimuli and is a critical component in the regulation of G(1) to S phase progression of the cell cycle. Angiotensin II (Ang II) binds to specific G protein-coupled receptors and is mitogenic in Chinese hamster ovary cells stably expressing the rat vascular Ang II type 1A receptor (CHO-AT(1A)). We recently reported that in these cells, Ang II induced cyclin D1 promoter activation and protein expression in a phosphatidylinositol 3-kinase (PI3K)-, SHP-2-, and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK)-dependent manner (Guillemot, L., Levy, A., Zhao, Z. J., B??r??ziat, G., and Rothhut, B. (2000) J. Biol. Chem. 275, 26349-26358). In this report, transfection studies using a series of deleted cyclin D1 promoters revealed that two regions between base pairs (bp) -136 and -96 and between bp -29 and +139 of the human cyclin D1 promoter contained regulatory elements required for Ang II-mediated induction. Mutational analysis in the -136 to -96 bp region provided evidence that a Sp1/early growth response protein (Egr) motif was responsible for cyclin D1 promoter activation by Ang II. Gel shift and supershift studies showed that Ang II-induced Egr-1 binding involved de novo protein synthesis and correlated well with Egr-1 promoter activation. Both U0126 (an inhibitor of the MAPK/ERK kinase MEK) and wortmannin (an inhibitor of PI3K) abrogated Egr-1 endogenous expression and Egr-1 promoter activity induced by Ang II. Moreover, using a co-transfection approach, we found that Ang II induction of Egr-1 promoter activity was blocked by dominant-negative p21(ras), Raf-1, and tyrosine phosphatase SHP-2 mutants. Identical effects were obtained when inhibitors and dominant negative mutants were tested on the -29 to +139 bp region of the cyclin D1 promoter. Taken together, these findings demonstrate that Ang II-induced cyclin D1 up-regulation is mediated by the activation and specific interaction of Egr-1 with the -136 to -96 bp region of the cyclin D1 promoter and by activation of the -29 to +139 bp region, both in a p21(ras)/Raf-1/MEK/ERK-dependent manner, and also involves PI3K and SHP-2.";
prov:wasQuotedFrom pubmed:11502738 .
sub:_5 rdfs:label "Selventa" .
sub:assertion prov:hadPrimarySource pubmed:11502738;
prov:wasDerivedFrom beldoc:, sub:_4 .
}
sub:pubinfo {
this: dcterms:created "2014-07-03T14:29:57.835+02:00"^^xsd:dateTime;
pav:createdBy orcid:0000-0001-6818-334X, orcid:0000-0002-1267-0234 .
}