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Originally published In Press as doi:10.1074/jbc.M507503200 on August 26, 2005

J. Biol. Chem., Vol. 280, Issue 43, 36007-36012, October 28, 2005
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Cadherins Mediate Both the Association between PS1 and {beta}-Catenin and the Effects of PS1 on {beta}-Catenin Stability*

Geo Serban1, Zen Kouchi, Lia Baki, Anastasios Georgakopoulos, Claudia M. Litterst, Junichi Shioi, and Nikolaos K. Robakis2

From the Departments of Psychiatry and Neuroscience, Mount Sinai School of Medicine, New York University, New York, New York 10029

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.


Received for publication, July 11, 2005 , and in revised form, August 15, 2005.

* This work was supported by National Institutes of Health Grants AG-17926 and AG-08200. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 Present address: Dept. of Pathology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

2 To whom correspondence should be addressed: Dept. of Psychiatry and Neuroscience, Mount Sinai School of Medicine, New York University, New York, NY 10029. Tel.: 212-241-9380; Fax: 212-831-1947; E-mail: nikos.robakis{at}mssm.edu.


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[Abstract] [Full Text] [PDF]




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