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TAZ, a Transcriptional Modulator of Mesenchymal Stem Cell Differentiation
Hong, Jeong-Ho,Hwang, Eun-Sook,McManus, Michael T.,Amsterdam, Adam,Tian, Yu,Kalmukova, Ralitsa,Mueller, Elisabetta,Benjamin, Thomas,Spiegelman, Bruce M.,Sharp, Phillip A.,Hopkins, Nancy,Yaffe, Michael 이화여자대학교 약학연구소 2005 藥學硏究論文集 Vol.- No.16
Mesenchymal stem celts (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome protiferator-activated receptor γ(PPARγ), drive MSCs to differentiate into either osteoblasts or adipocytes, respectively. How these two transcription factors are regulated in order to specify these alternate cell fates remains a pivotal question. Here we report that a 14-3-3-binding protein, TAZ(transcrip-tional coactivator with PDZ-binding motif), coactivates RunxB-dependent gene transcription while repressing PPARγ-dependent gene transcription. By modulating TAZ expression in model cell lines, mouse embryonic fibroblasts, and primary MSCs in culture and in zebrafish in vivo, we observed alterations in osteogenic versus adipogenic potential. These results indicate that TAZ functions as a molecular rheostat that modulates MSC differentiation.