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TAZ, a Transcriptional Modulator of Mesenchymal Stem Cell Differentiation
Ist Teil von
Science (American Association for the Advancement of Science), 2005-08, Vol.309 (5737), p.1074-1078
Ort / Verlag
Washington, DC: American Association for the Advancement of Science
Erscheinungsjahr
2005
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
Mesenchymal stem cells (MSCs) are a pluripotent cell type that can differentiate into several distinct lineages. Two key transcription factors, Runx2 and peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]), 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 (transcriptional coactivator with PDZ-binding motif), coactivates Runx2-dependent gene transcription while repressing PPAR[gamma]-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.