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

J Biol Chem. 2002 Jan 11;277(2):1120-7. doi: 10.1074/jbc.M109912200. Epub 2001 Nov 5.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Adenoviridae / metabolism
  • Animals
  • Cell Line
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation, Developmental / physiology*
  • Hair Follicle / cytology
  • Hair Follicle / growth & development
  • Hair Follicle / metabolism
  • Humans
  • Lymphoid Enhancer-Binding Factor 1
  • Mesoderm / cytology
  • Mesoderm / metabolism
  • Mice
  • Neural Cell Adhesion Molecules / genetics*
  • Neural Cell Adhesion Molecules / metabolism
  • Precipitin Tests
  • Promoter Regions, Genetic / physiology*
  • Protein Binding
  • Protein Structure, Tertiary
  • Proteins / metabolism*
  • Recombinant Fusion Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • ALX4 protein, human
  • DNA-Binding Proteins
  • LEF1 protein, human
  • Lef1 protein, mouse
  • Lymphoid Enhancer-Binding Factor 1
  • Neural Cell Adhesion Molecules
  • Proteins
  • Recombinant Fusion Proteins
  • Transcription Factors