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All rights reserved. http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM#_5 http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://purl.org/pav/version 20131211 http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM#_4 http://www.w3.org/ns/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. http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM#_4 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/11502738 http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM#_5 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/11502738 http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/20131211/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM#_4 http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM#pubinfo http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM http://purl.org/dc/terms/created 2014-07-03T14:31:43.165+02:00 http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RAI8TRUUWRkyLQQYN4mZfO_JwOAGJ4ZyZu93rWfd29xVM http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234