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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

Tomoki Yano, Yuji Yamazaki, Makoto Adachi, Katsuya Okawa, Philippe Fort, Masami Uji, Shoichiro Tsukita, Sachiko Tsukita

J Cell Biol. 2011 Apr 18;193(2):319-32.

PMID: 21482718

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP347323960	ITX3		347323-96-0	Price

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