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Papers In Press, published online ahead of print November 5, 2001
J. Biol. Chem, 10.1074/jbc.M109912200
Submitted on October 12, 2001
Revised on November 5, 2001
Accepted on November 5, 2001

Alx4 binding to LEF-1 regulates N-CAM promoter activity

Kata Boras and Paul A. Hamel

Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5S 1A8

Corresponding Author: paul.hamel{at}utoronto.ca

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 their 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, the HMG-box, of LEF-1. We also demonstrate that LEF-1 and Alx4 can bind simultaneously to adjacent sites on the 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 giving rise to mesenchymal-specific activities of LEF-1.


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