LEF1 and TCF are members of the high mobility group (HMG) DNA-binding protein family of transcription factors that consists of the following: Lymphoid Enhancer Factor 1 (LEF1), T Cell Factor 1 (TCF1/TCF7), TCF3/TCF7L1, and TCF4/TCF7L2. LEF1 and TCF1/TCF7 were originally identified as important factors that regulate early lymphoid development and act downstream in Wnt signaling. LEF1 and TCF bind to Wnt response elements to provide docking sites for -catenin, which translocates to the nucleus to promote the transcription of target genes upon activation of Wnt signaling. LEF1 and TCF are dynamically expressed during development and aberrant activation of the Wnt signaling pathway is involved in many types of cancers, including colon cancer. LEF1 has several isoforms due to alternative splicing. LEF1 also has an alternative promoter that is preferentially active in lymphocytes. The isoforms generated by this alternative promoter have no amino-terminal -catenin binding domain and may function in a dominant negative manner.
