Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability |
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Authors: | Serban Geo Kouchi Zen Baki Lia Georgakopoulos Anastasios Litterst Claudia M Shioi Junichi Robakis Nikolaos K |
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Institution: | Department of Psychiatry, Mount Sinai School of Medicine, New York University, New York, New York 10029, USA. |
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Abstract: | Presenilin1 (PS1), a protein involved in cellular development, forms functional complexes with beta-catenin, a regulator of Wnt signaling and cell-cell adhesion. In addition, both proteins have been shown to play important roles in disease including cancer and Alzheimer disease. Although PS1 and beta-catenin are found in the same complexes, it is not clear whether they bind directly to each other or a third complex component, like cadherin, may mediate their interactions. Here we show that PS1 and beta-catenin form no detectable complexes in cells that express no cadherin. In contrast, these complexes are readily found in E-cadherin containing cells. Furthermore, binding of both PS1 and beta-catenin to E-cadherin is necessary for the formation of PS1/beta-catenin complexes. Importantly, our data show that binding of PS1 to cadherin mediates the effects of PS1 on the phosphorylation, ubiquitination, and destabilization of beta-catenin. Thus, cadherins mediate both the association of PS1 and beta-catenin and the effects of PS1 on the cellular levels of beta-catenin. |
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