Abstract
LEF/TCF transcription factors are nuclear mediators of beta‐catenin‐dependent Wnt signaling. While all LEF/TCFs direct Wnt signals to target genes for regulation, mammalian members of this family also exhibit differences in DNA sequence recognition, dominant negative actions and nuclear/cytoplasmic shuttling. These non‐redundant activities modify the strength and specificity of Wnt signals in the nucleus. Alternative splicing and promoter usage drive some of these non‐redundancies, but the nuclear/cytoplasmic shuttling activity derives from a signal transduction cascade first defined in C. elegans for guiding differential cell fate choices during development. This pathway can be triggered by specific Wnt ligands or calcium calmodulin kinase II. In addition, it functions as a Wnt signaling loop as it can trigger the release of Wnt ligands from cells. The biological consequences of this pathway will be discussed in relation to the expression patterns of LEF/TCFs in development and disease.
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