YBX1 is a modulator of MIA/CD-RAP-dependent chondrogenesis.

YBX1 is a modulator of MIA/CD-RAP-dependent chondrogenesis.
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DOI:
10.1371/journal.pone.0082166
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Bosserhoff AK
Bosserhoff AK
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Schmid R;Meyer K;Spang R;Schittek B;Bosserhoff AK

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MIA/CD-RAP是一种小的、分泌的蛋白质,参与软骨分化和黑色素瘤的进展。我们最近发现p54nrb在MIA/CD-RAP促进软骨生成和恶性黑色素瘤进展的作用中起中介作用。由于目前MIA/CD-RAP在软骨中作用的分子机制尚未明确,本研究旨在了解p54nrb转录在软骨形成中的调控作用。我们集中在先前描述的p54nrb启动子中依赖于MIA/CD-RAP的调控区,并研究了MIA/CD-RAP对软骨中p54nrb的转录调控。一系列截短的p54nrb启动子结构和突变分析表明,转录因子YBX1是依赖MIA/CD-RAP激活p54nrb转录的中介因子,目前为止还没有关于软骨形成的研究。对启动子区域携带该结合位点的基因的系统分析进一步揭示了与软骨分化有关的潜在的MIA/CD-RAP调控基因。综上所述,我们描述了MIA/CD-RAP对软骨细胞转录调控的影响。了解p54nrb通过YBX1的调控有助于理解软骨形成。通过激活YBX1发现新的下游效应器,支持MIA/CD-RAP在这些过程中的重要作用。
MIA/CD-RAP is a small, secreted protein involved in cartilage differentiation and melanoma progression. We recently revealed that p54nrb 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 p54nrb transcription in chondrogenesis. We concentrated on the previously described MIA/CD-RAP-dependent regulatory region in the p54nrb promoter and characterized the transcriptional regulation of p54nrb by MIA/CD-RAP in cartilage. A series of truncated p54nrb 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 p54nrb 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 p54nrb 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.
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