A novel isoform of human lymphoid enhancer-binding factor-1 [LEF-1] gene transcript encodes a protein devoid of HMG domain and nuclear localization signal

Lymphoid enhancer-binding factor-1 (LEF-1), a member of the high mobility group (HMG) family of proteins, regulates expression of T-cell receptor-a gene and is one of the key regulatory molecules in the epithelial-mesenchymal interactions during embryonic de­velopment. Among others, LEF-1 regulates expression of cytokeratin genes involved in formation of hair follicles and the gene encoding the cell-adhesion molecule E-cadherin. Transcription factor LEF-1, which acts as a dimer, binds ß-catenin and is involved in signal transduction by the wnt pathway. We have cloned and sequenced a novel isoform of human LEF-1 gene transcript. This isoform encodes a truncated protein devoid of HMG domain and nuclear localization sig­nal but retaining ß-catenin binding domain. This isoform might either act in a domi­nant-negative manner by interfering with native LEF-1, or might bind ß-catenin in the cytosol, which would result in attenuation of the signals transmitted by theLEF-ß-catenin pathway.