@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 scomp: .
@prefix ProteinComplex: .
@prefix hasAgent: .
@prefix RNA: .
@prefix hgnc: .
@prefix geneProductOf: .
@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 {
scomp:AP-1%20Complex a ProteinComplex: .
sub:_1 hasAgent: scomp:AP-1%20Complex;
a go:0042789 .
sub:_2 geneProductOf: hgnc:16;
a RNA: .
sub:_3 occursIn: species:9606;
rdf:object sub:_2;
rdf:predicate belv:increases;
rdf:subject sub:_1;
a rdf:Statement .
sub:assertion rdfs:label "tscript(complex(SCOMP:\"AP-1 Complex\")) -> r(HGNC:SERPINA3)" .
}
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 "20131211" .
sub:_4 prov:value "The expression of alpha(1)-antichymotrypsin (ACT) is significantly enhanced in affected brain regions in Alzheimer's disease. This serine proteinase inhibitor specifically colocalizes with filamentous beta-amyloid deposits and recently has been shown to influence both formation and destabilization of beta-amyloid fibrils. In the brain, ACT is expressed in astrocytes, and interleukin-1 (IL-1), tumor necrosis factor alpha (TNF), oncostatin M (OSM), and IL-6/soluble IL-6 receptor complexes control synthesis of this inhibitor. Here, we characterize a molecular mechanism responsible for both IL-1 and TNF-induced expression of ACT gene in astrocytes. We identify the 5' distal IL-1/TNF-responsive enhancer of the ACT gene located 13 kb upstream of the transcription start site. This 413-bp-long enhancer contains three elements, two of which bind nuclear factor kB (NF-kB) and one that binds activating protein 1 (AP-1). All of these elements contribute to the full responsiveness of the ACT gene to both cytokines, as determined by deletion and mutational analysis. The 5' NF-kB high-affinity binding site and AP-1 element contribute most to the enhancement of gene transcription in response to TNF and IL-1. In addition, we demonstrate that the 5' untranslated region of the ACT mRNA does not contribute to cytokine-mediated activation. Finally, we find that overexpression of the NF-kB inhibitor (IkB) totally inhibits any activation mediated by the newly identified IL-1/TNF enhancer of the ACT gene.";
prov:wasQuotedFrom pubmed:11027208 .
sub:_5 rdfs:label "Selventa" .
sub:assertion prov:hadPrimarySource pubmed:11027208;
prov:wasDerivedFrom beldoc:, sub:_4 .
}
sub:pubinfo {
this: dcterms:created "2014-07-03T14:31:37.441+02:00"^^xsd:dateTime;
pav:createdBy orcid:0000-0001-6818-334X, orcid:0000-0002-1267-0234 .
}