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Originally published In Press as doi:10.1074/jbc.M109912200 on November 5, 2001

J. Biol. Chem., Vol. 277, Issue 2, 1120-1127, January 11, 2002
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Alx4 Binding to LEF-1 Regulates N-CAM Promoter Activity*

Kata Boras and Paul A. HamelDagger

From the Department of Laboratory Medicine and Pathobiology, University of Toronto, Ontario M5S 1A8, Canada

During murine embryogenesis, expression of the paired-like homeodomain protein Alx4 is restricted to tissues whose development depends on the expression of lymphoid enhancer factor-1 (LEF-1). Given the defects seen in hair follicle development in both LEF-1 and Alx4 knockout and mutant animals and the overlapping expression patterns, we predicted that LEF-1 and Alx4 might form physical complexes. We demonstrate here the interaction between LEF-1 and Alx4. This interaction is mediated through a specific proline-rich domain in the N-terminal region of Alx4 and requires the DNA-binding domain (HMG-box) of LEF-1. We also demonstrate that LEF-1 and Alx4 can bind simultaneously to adjacent sites on the neural cell adhesion molecule (N-CAM) promoter and that this binding alters N-CAM promoter activity. Furthermore, when expressed in primary mammary stromal cells, Alx4 decreases the expression of endogenous N-CAM protein. These results reveal a potential mechanism that gives rise to mesenchymal-specific activities of LEF-1.


* This work was supported by a grant from the National Cancer Institute of Canada with support from the Canadian Cancer Society (to P. A. H.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Rm. 6318, Medical Sciences Bldg., University of Toronto, Ontario M5S 1A8, Canada. Tel.: 416-978-8741; Fax: 416-978-5959; E-mail: paul.hamel@utoronto.ca.


Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.