title: YBX1 is a modulator of MIA/CD-RAP-dependent chondrogenesis.
abstract: MIA/CD-RAP is a small, secreted protein involved in cartilage differentiation and melanoma progression. We recently revealed that p54(nrb) acts as a mediator of MIA/CD-RAP action to promote chondrogenesis and the progression of malignant melanoma. As the molecular mechanism of MIA/CD-RAP action in cartilage has not been defined in detail until now, we aimed to understand the regulation of p54(nrb) transcription in chondrogenesis. We concentrated on the previously described MIA/CD-RAP-dependent regulatory region in the p54(nrb) promoter and characterized the transcriptional regulation of p54(nrb) by MIA/CD-RAP in cartilage. A series of truncated p54(nrb) promoter constructs and mutagenesis analysis revealed that the transcription factor YBX1, which has not been investigated in chondrogenesis thus far, is the mediator of MIA/CD-RAP dependent activation of p54(nrb) transcription. A systematic analysis of genes carrying this binding site in their promoter region revealed further potential MIA/CD-RAP-regulated genes that have been implicated in cartilage differentiation. In summary, we described the effects of MIA/CD-RAP on transcriptional regulation in chondrocytes. Understanding the regulation of p54(nrb) via YBX1 contributes to the understanding of chondrogenesis. Uncovering new downstream effectors that function via the activation of YBX1 supports the important role of MIA/CD-RAP in these processes.
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Schmid
authors.affiliation: Institute for Functional Genomics, University of Regensburg, Regensburg, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Meyer
authors.affiliation: Institute for Functional Genomics, University of Regensburg, Regensburg, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spang
authors.affiliation: Institute of Dermatology, University of Tübingen, Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schittek
authors.affiliation: Institute of Pathology, University of Regensburg, Regensburg, Germany.
authors.forename: Anja Katrin
authors.initials: AK
authors.lastname: Bosserhoff
mesh_terms: D000818:Animals; D020029:Base Pairing / Q000235:genetics; D001665:Binding Sites; D002356:Cartilage / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D020219:Chondrogenesis / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000378:metabolism*; D034521:Nuclear Matrix-Associated Proteins / Q000235:genetics / Q000378:metabolism; D050810:Octamer Transcription Factors / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D051840:Y-Box-Binding Protein 1 / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D034521:Nuclear Matrix-Associated Proteins; D050810:Octamer Transcription Factors; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D051840:Y-Box-Binding Protein 1; C090059:MIA protein, human; C513263:Mia protein, mouse; C083214:NONO protein, human; C541744:Ybx1 protein, mouse; C070856:YBX1 protein, human; C500331:Nono protein, mouse