title: Melanoma inhibitory activity promotes melanoma development through activation of YBX1.
abstract: Melanoma inhibitory activity (MIA), a small soluble secreted protein, is functionally important for progression of malignant melanoma. We recently revealed that p54(nrb) acts as a mediator of MIA action. In this study, we characterize the transcriptional regulation of p54(nrb) by MIA to explain MIA's molecular action. We identified one highly conserved region in the p54(nrb) promoter that is necessary and sufficient for MIA-dependent activation. Functional promoter analysis identified the transcription factor YBX1 as the mediator of MIA activation of p54(nrb) transcription. We screened the genome for further potential MIA-regulated genes carrying the element in their promoter regions. Integrating our sequence data with expression data from human melanomas identified a list of 23 potential MIA-YBX1 targets in melanomas. In summary, we present for the first time effects of MIA on transcriptional regulation. Uncovering new potential downstream effectors working via activation of YBX1 supports the important role of MIA in melanoma.
authors.affiliation: Institute of Pathology, University of Regensburg Medical School, Regensburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schmid
authors.forename: Katharina
authors.initials: K
authors.lastname: Meyer
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
authors.forename: Birgit
authors.initials: B
authors.lastname: Schittek
authors.forename: Anja-Katrin
authors.initials: AK
authors.lastname: Bosserhoff
mesh_terms: D000818:Animals; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D063646:Carcinogenesis / Q000235:genetics / Q000473:pathology*; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins; D018450:Disease Progression; D024202:Electrophoretic Mobility Shift Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000378:metabolism*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics; D050810:Octamer Transcription Factors / Q000235:genetics; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051840:Y-Box-Binding Protein 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; C090059:MIA protein, human; C083214:NONO protein, human; D009363:Neoplasm Proteins; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human
keywords: MIA; melanoma progression; p54nrb promoter regulation; target gene prediction