title: The increased Sprouty4 expression in response to serum is transcriptionally controlled by Specific protein 1.
abstract: Sprouty proteins control length and intensity of the intracellular signal transduction cascade activated by mitogens in the cellular environment. As part of a negative feedback loop, their expression is supposed to be elevated by the same factors. In this report, Sprouty4 expression in response to serum and the underlying regulatory mechanisms were investigated. We verified that Sprouty4 expression is activated by serum addition in all tested cells independent of their origin. Strict correlation between Sprouty4 protein levels and promoter activity indicates mainly transcriptional regulation of Sprouty4 serum-responsiveness. Induction of the mitogen-activated protein kinase pathway is required for Sprouty4 promoter activation in the presence of serum. Nonetheless, signal transduction via this pathway is not sufficient to fully induce the Sprouty4 promoter. Instead, deletion and mutation analysis identified two annotated Specific protein 1 binding sites as the critical cis-elements responsible for conferring the serum induction of the promoter. Corroborating, repressed Specific protein 1 activity or levels result in constitutive lowered transcriptional activity of the Sprouty4 promoter. These data demonstrate that Specific protein 1 plays a crucial role in the regulation of Sprouty4 in response to serum.
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Electronic address: angelina.doriguzzi@meduniwien.ac.at.
authors.forename: Angelina
authors.initials: A
authors.lastname: Doriguzzi
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Electronic address: barbara.haigl@gmx.at.
authors.forename: Barbara
authors.initials: B
authors.lastname: Haigl
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Electronic address: andrea.gsur@meduniwien.ac.at.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gsur
authors.affiliation: Institute of Cancer Research, Department of Medicine I, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria. Electronic address: hedwig.sutterluety-fall@meduniwien.ac.at.
authors.forename: Hedwig
authors.initials: H
authors.lastname: Sutterlüty-Fall
mesh_terms: D001665:Binding Sites; D003470:Culture Media; D004789:Enzyme Activation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D061986:MCF-7 Cells; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000502:physiology*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
chemical_list: D003470:Culture Media; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C499038:SPRY4 protein, human; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; D020928:Mitogen-Activated Protein Kinases
keywords: Negative feedback loop; Serum response; Sp1; Specific protein 1; Sprouty4 promoter