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All rights reserved. http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/dc/elements/1.1/title BEL Framework Large Corpus Document http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/authoredBy http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM#_6 http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://purl.org/pav/version 1.4 http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM#_5 http://www.w3.org/ns/prov#value Here we identify the paired-like homeobox transcription factors Pitx1 and Pitx2 as factors functionally activating the proximal human prolactin promoter (hPRL-164luc). Using in vitro binding assays and a series of site-specific mutations of the proximal hPRL promoter, we mapped the B1 and B2 bicoid sites involved in Pitx-mediated transactivation of the hPRL-164luc construct. In somatolactotroph GH4C1 cells, basal proximal hPRL promoter activity was inhibited by a Pitx2 dominant-negative form in a dose-dependent manner, whereas binding disruptive mutations in the Pitx sites significantly reduced basal activity of the promoter. We also show that synergistic activation of hPRL-164luc by Pitx2 and Pit-1 requires the integrity of the B2 Pitx binding site, and at least one of the P1 and P2 Pit-1 response elements. In addition, mutation in the B2 Pitx site results in attenuation of the promoter's responsiveness to forskolin, thyrotropin-releasing hormone, and epidermal growth factor. Conversely, Pitx1 or Pitx2 overexpression in GH4C1 cells leads to an enhancement of the drugs stimulatory effects.). http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM#_5 http://www.w3.org/ns/prov#wasQuotedFrom http://www.ncbi.nlm.nih.gov/pubmed/12223489 http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM#_6 http://www.w3.org/2000/01/rdf-schema#label Selventa http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM#assertion http://www.w3.org/ns/prov#hadPrimarySource http://www.ncbi.nlm.nih.gov/pubmed/12223489 http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://resource.belframework.org/belframework/1.0/knowledge/large_corpus.bel http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM#assertion http://www.w3.org/ns/prov#wasDerivedFrom http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM#_5 http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM#pubinfo http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM http://purl.org/dc/terms/created 2014-07-03T14:30:05.710+02:00 http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM http://purl.org/pav/createdBy http://orcid.org/0000-0001-6818-334X http://www.tkuhn.ch/bel2nanopub/RABGEyZY6KOedEhdFzQTb1-Oy8qHGXThB02rf2wAe8mQM http://purl.org/pav/createdBy http://orcid.org/0000-0002-1267-0234