Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling.
Tara up-regulates E-cadherin transcription by binding to the Trio RhoGEF and inhibiting Rac signaling.
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DOI：
10.1083/jcb.201009100
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发表时间：
2011-04-18
期刊：
影响因子：
--
通讯作者：
Tsukita S
中科院分区：
文献类型：
--
作者：
Yano T;Yamazaki Y;Adachi M;Okawa K;Fort P;Uji M;Tsukita S;Tsukita S
在不存在塔拉的情况下，Trio与E-钙粘蛋白结合并增加E-钙粘蛋白转录抑制因子Tbx 3的激活。E-cadherin表达的时空调控在机体发育和癌变过程中具有重要意义。我们发现塔拉（Trio-associated repeat on actin）在基于钙粘蛋白的粘附连接（adherens junctions，AJs）中富集，并且在MDCK细胞（Tara-KD细胞）中其敲低显著降低E-钙粘蛋白的表达。Tara-KD通过Trio RhoGEF激活Rac 1，Rac 1与E-钙粘蛋白结合，随后增加p38和Tbx 3（一种转录E-钙粘蛋白阻遏物）的磷酸化。因此，E-钙粘蛋白表达的减少被ITX 3和SB 203580（分别为Trio RhoGEF和p38 MAPK的特异性抑制剂）和脱磷酸模拟物Tbx 3消除。尽管E-钙粘蛋白表达降低，但Tara-KD细胞不经历上皮-间充质转化并保持为上皮细胞片，这可能是由于钙粘蛋白-6的伴随上调。Tara-KD降低了周向环中的肌动蛋白带密度，并且细胞形成扁平囊肿，这表明塔拉通过上调E-钙粘蛋白转录来调节上皮细胞片层的形成和完整性。
In the absence of Tara, Trio binds to E-cadherin and increases activation of the E-cadherin transcriptional repressor Tbx3. The spatiotemporal regulation of E-cadherin expression is important during body plan development and carcinogenesis. We found that Tara (Trio-associated repeat on actin) is enriched in cadherin-based adherens junctions (AJs), and its knockdown in MDCK cells (Tara-KD cells) significantly decreases the expression of E-cadherin. Tara-KD activates Rac1 through the Trio RhoGEF, which binds to E-cadherin and subsequently increases the phosphorylation of p38 and Tbx3, a transcriptional E-cadherin repressor. Accordingly, the decrease in E-cadherin expression is abrogated by ITX3 and SB203580 (specific inhibitors of Trio RhoGEF and p38MAPK, respectively), and by dephosphomimetic Tbx3. Despite the decreased E-cadherin expression, the Tara-KD cells do not undergo an epithelial–mesenchymal transition and remain as an epithelial cell sheet, presumably due to the concomitant up-regulation of cadherin-6. Tara-KD reduces the actin-belt density in the circumferential ring, and the cells form flattened cysts, suggesting that Tara functions to modulate epithelial cell sheet formation and integrity by up-regulating E-cadherin transcription.
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影响因子：
8
作者：
Jeanes, A.;Gottardi, C. J.;Yap, A. S.
通讯作者：
Yap, A. S.
DOI：
10.1083/jcb.200612080
发表时间：
2007-03-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ikenouchi J;Umeda K;Tsukita S;Furuse M;Tsukita S
通讯作者：
Tsukita S
影响因子：
5.5
作者：
Khanna, Payal;Yunkunis, Tara;Dong, Cheng
通讯作者：
Dong, Cheng
影响因子：
4
作者：
Ikenouchi, J;Matsuda, M;Tsukita, S
通讯作者：
Tsukita, S
DOI：
10.1073/pnas.93.11.5466
发表时间：
1996-05-28
影响因子：
11.1
作者：
Debant, A;SerraPages, C;Streuli, M
通讯作者：
Streuli, M