Publikation: Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex
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In epithelial cells, tyrosine kinases induce the tyrosine phosphorylation and ubiquitination of the E-cadherin complex, which induces endocytosis of E-cadherin. With a modified yeast 2-hybrid system, we isolated Hakai, an E-cadherin binding protein, which we have identified as an E3 ubiquitin-ligase. Hakai contains SH2, RING, zinc-finger and proline-rich domains, and interacts with E-cadherin in a tyrosine phosphorylation-dependent manner, inducing ubiquitination of the E-cadherin complex. Expression of Hakai in epithelial cells disrupts cell--cell contacts and enhances endocytosis of E-cadherin and cell motility. Through dynamic recycling of E-cadherin, Hakai can thus modulate cell adhesion, and could participate in the regulation of epithelial--mesenchymal transitions in development or metastasis.
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FUJITA, Yasuyuki, Gerd KRAUSE, Martin SCHEFFNER, Dietmar ZECHNER, Hugo E Molina LEDDY, Jürgen BEHRENS, Thomas SOMMER, Walter BIRCHMEIER, 2002. Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex. In: Nature cell biology. 2002, 4(3), pp. 222-231. ISSN 1465-7392. eISSN 1476-4679. Available under: doi: 10.1038/ncb758BibTex
@article{Fujita2002-03Hakai-42453, year={2002}, doi={10.1038/ncb758}, title={Hakai, a c-Cbl-like protein, ubiquitinates and induces endocytosis of the E-cadherin complex}, number={3}, volume={4}, issn={1465-7392}, journal={Nature cell biology}, pages={222--231}, author={Fujita, Yasuyuki and Krause, Gerd and Scheffner, Martin and Zechner, Dietmar and Leddy, Hugo E Molina and Behrens, Jürgen and Sommer, Thomas and Birchmeier, Walter} }
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