Interaction of LEF1 with TAZ is necessary for the osteoblastogenic activity of Wnt3a.
Interaction of LEF1 with TAZ is necessary for the osteoblastogenic activity of Wnt3a.
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DOI：
10.1038/s41598-018-28711-4
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发表时间：
2018-07-10
影响因子：
4.6
通讯作者：
Nishimura R
中科院分区：
文献类型：
--
作者：
Kida J;Hata K;Nakamura E;Yagi H;Takahata Y;Murakami T;Maeda Y;Nishimura R
经典Wnt信号在成骨细胞分化和骨形成中起重要作用。然而，经典Wnt信号传导发挥其成骨细胞作用的分子机制仍然难以捉摸。在这里，我们研究了淋巴增强子结合因子1（LEF1）和PDZ结合基序（TAZ）的转录共激活因子之间的关系，这两者都是成骨细胞分化过程中介导经典Wnt信号传导的转录调节因子。报告分析和免疫共沉淀实验揭示了LEF1和TAZ之间的功能和物理相互作用。LEF1或TAZ的显性阴性形式的过表达显著抑制Wnt3a依赖的成骨细胞分化。此外，我们发现，LEF1和TAZ形成了一个转录复合物与runt相关的转录因子2（Runx2）和抑制LEF1或TAZ的显性负性形式显着抑制成骨细胞活性的Ruxn2。此外，Wnt3a增强骨形态发生蛋白2（BMP 2）诱导的成骨细胞分化，BMP 2通过调节Runx2刺激成骨细胞分化。总的来说，这些发现表明LEF1和TAZ之间的相互作用对于Wnt3a的成骨细胞活性是至关重要的，并且LEF1和TAZ通过与Runx2的结合促进Wnt3a和BMP 2对成骨细胞分化的协同作用。
Canonical Wnt signalling plays an important role in osteoblast differentiation and bone formation. However, the molecular mechanisms by which canonical Wnt signalling exerts its osteoblastogenic effect remain elusive. Here, we investigated the relationship between lymphoid enhancer-binding factor 1 (LEF1) and transcriptional co-activator with PDZ-binding motif (TAZ), both of which are transcriptional regulators that mediate canonical Wnt signalling during osteoblast differentiation. Reporter assay and co-immunoprecipitation experiments revealed functional and physical interaction between LEF1 and TAZ. Overexpression of dominant-negative forms of either LEF1 or TAZ markedly inhibited Wnt3a-dependent osteoblast differentiation. Moreover, we found that LEF1 and TAZ formed a transcriptional complex with runt-related transcription factor 2 (Runx2) and that inhibition of LEF1 or TAZ by their dominant-negative forms dramatically suppressed the osteoblastogenic activity of Ruxn2. Additionally, Wnt3a enhanced osteoblast differentiation induced by bone morphogenetic protein 2 (BMP2), which stimulates osteoblast differentiation by regulating Runx2. Collectively, these findings suggest that interaction between LEF1 and TAZ is crucial for the osteoblastogenic activity of Wnt3a and that LEF1 and TAZ contribute to the cooperative effect of Wnt3a and BMP2 on osteoblast differentiation through association with Runx2.
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影响因子：
10.5
作者：
Meng Z;Moroishi T;Guan KL
通讯作者：
Guan KL
影响因子：
4.8
作者：
Nakashima, A;Katagiri, T;Tamura, M
通讯作者：
Tamura, M
影响因子：
64.5
作者：
Gong, YQ;Slee, RB;Warman, ML
通讯作者：
Warman, ML
DOI：
10.1038/nrm.2015.3
发表时间：
2016-01
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
McCrea PD;Gottardi CJ
通讯作者：
Gottardi CJ
影响因子：
56.9
作者：
Hong, JH;Hwang, ES;Yaffe, MB
通讯作者：
Yaffe, MB