Publications (5)23.33 Total impact
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Article: TAZ suppresses NFAT5 activity through tyrosine phosphorylation.
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ABSTRACT: Transcriptional co-activator with PDZ-binding motif (TAZ) physically interacts with a variety of transcription factors and modulates their activities involved in cell proliferation and mesenchymal stem cell differentiation. TAZ is highly expressed in the kidney and its deficiency displays multiple renal cysts and urinary concentration defects; however, the molecular functions of TAZ in renal cells remain largely unknown. Here, we examined the effects of osmotic stress on TAZ expression and activity in renal cells. We found that hyperosmotic stress selectively increased protein phosphorylation at tyrosine 316 of TAZ, which was enhanced by c-Abl activation in response to hyperosmotic stress. Of interest, the phosphorylated TAZ physically interacted with nuclear factor of activated T-cells 5 (NFAT5), a major osmoregulatory transcription factor, and subsequently suppressed DNA binding and transcriptional activity of NFAT5. Furthermore, TAZ deficiency elicited an increase in NFAT5 activity in vitro and in vivo, which then reverted to basal levels following restoration of wild-type TAZ, but not the mutant TAZ (Y316F). Collectively, we suggest that TAZ modulates cellular responses to hyperosmotic stress through fine-tuning of NFAT5 activity via tyrosine phosphorylation.Molecular and cellular biology 10/2012; · 6.06 Impact Factor -
Article: TAZ is required for the osteogenic and anti-adipogenic activities of kaempferol.
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ABSTRACT: Kaempferol (KMP) exerts protective effects against both osteoporosis and obesity by regulating cellular activities, but the underlying molecular mechanisms have not been fully elucidated. TAZ (transcriptional coactivator with PDZ-binding motif) modulates both osteoblast and adipocyte differentiation from mesenchymal stem cells by stimulating the activities of RUNX2 (runt-related transcription factor 2) and suppressing the activities of PPARγ (peroxisome proliferator-activated receptor γ). In this study, we investigated the effects of KMP on TAZ regulated osteoblast and adipocyte differentiation. KMP increased the osteoblast differentiation of mesenchymal cells by facilitating the physical interaction between TAZ and RUNX2, thus the increasing transcriptional activities of RUNX2. KMP also enhanced the association of TAZ with PPARγ, thereby suppressing the gene transcription of PPARγ targets and resulting in diminished adipocyte differentiation. Interestingly, the regulatory effects of kaempferol on RUNX2 and PPARγ-mediated transcriptional activity were impaired in TAZ-null mouse embryonic fibroblasts but recovered by restoration of TAZ expression. Our results demonstrate that KMP fortifies TAZ activity, which enhances RUNX2-mediated osteoblast differentiation and suppresses PPARγ-stimulated adipocyte differentiation, indicating the potential of KMP as an effective therapeutic reagent for controlling bone loss and adiposity through TAZ activation.Bone 11/2011; 50(1):364-72. · 4.02 Impact Factor -
Article: Hesperedin promotes MyoD-induced myogenic differentiation in vitro and in vivo.
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ABSTRACT: The bioflavonoid, hesperedin, promotes osteoblast differentiation in human mesenchymal stem cells, indicating an anabolic effect of hesperedin on bone metabolism. Murine bone marrow mesenchymal stem cells undergo myogenic differentiation as well as osteogenic differentiation. We therefore explored whether hesperedin modulates muscle cell differentiation. Myoblast C2C12 cells were differentiated into muscle cells in the presence or absence of hesperedin. The effects of hesperedin on myogenic differentiation were determined by analysing specific muscle markers in vitro using reporter gene assays, immunoblotting, RT-PCR and DNA pull-down assays. In vivo, the effects of hesperedin were assessed using the freeze injury-induced muscle regeneration model in mice and daily injections of hesperedin for 6 days. Hesperedin promoted myogenic differentiation, in a dose-dependent manner, by increasing myogenin gene expression. MyoD-induced myogenin gene transcription was enhanced by hesperedin, as this bioflavonoid augmented the nuclear localization and myogenin promoter-binding of MyoD. In addition, hesperedin increased myogenin and muscle creatine kinase gene expression during myogenic differentiation from C3H10T1/2 mesenchymal stem cells in a MyoD-dependent manner and accelerated in vivo muscle regeneration induced by muscle injury. Our results demonstrate that hesperedin promoted myogenic differentiation in vitro and in vivo through activation of MyoD-mediated myogenin expression, suggesting a beneficial role in promoting muscle regeneration, following injury.British Journal of Pharmacology 01/2011; 163(3):598-608. · 4.41 Impact Factor -
Article: TAZ as a novel enhancer of MyoD-mediated myogenic differentiation.
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ABSTRACT: Myoblast differentiation is indispensable for skeletal muscle formation and is governed by the precisely coordinated regulation of a series of transcription factors, including MyoD and myogenin, and transcriptional coregulators. TAZ (transcriptional coactivator with PDZ-binding motif) has been characterized as a modulator of mesenchymal stem cell differentiation into osteoblasts and adipocytes through its regulation of lineage-specific master transcription factors. In this study, we investigated whether TAZ affects myoblast differentiation, which is one of the differentiated lineages of mesenchymal stem cells. Ectopic overexpression of TAZ in myoblasts increases myogenic gene expression in a MyoD-dependent manner and hastens myofiber formation, whereas TAZ knockdown delays myogenic differentiation. In addition, enforced coexpression of TAZ and MyoD in fibroblasts accelerates MyoD-induced myogenic differentiation. TAZ physically interacts with MyoD through the WW domain and activates MyoD-dependent gene transcription. TAZ additionally enhances the interaction of MyoD with the myogenin gene promoter. These results strongly suggest that TAZ functions as a novel transcriptional modulator of myogenic differentiation by promoting MyoD-mediated myogenic gene expression.The FASEB Journal 05/2010; 24(9):3310-20. · 5.71 Impact Factor -
Article: Identification of antiadipogenic constituents of the rhizomes of Anemarrhena asphodeloides.
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ABSTRACT: Three new phenolic compounds, (E)-4'-demethyl-6-methyleucomin (1), anemarcoumarin A (2), and anemarchalconyn (3), were isolated from an ethyl acetate extract of the rhizomes of Anemarrhena asphodeloides, together with seven known compounds (4-10). The structures of the new compounds (1-3) were determined on the basis of spectroscopic data interpretation. Compound 3 exhibited a potent inhibitory effect against the differentiation of preadipocyte 3T3-L1 cells with an IC50 value of 5.3 microM.Journal of Natural Products 09/2009; 72(10):1895-8. · 3.13 Impact Factor
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Institutions
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2010–2012
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Ewha Womans University
- Center for Cell Signaling and Drug Discovery Research
Seoul, Seoul, South Korea
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