TCF-1A Background Information T cell factor-1 (TCF-1) is a DNA-binding transcriptional activator that is essential for lymphoid cell development. The TCF family of transcription factors are activated by the Wnt-1 and Wingless pathways and are characterized by the presence of a conserved protein motif, the high mobility group (HMG) 1 box, which mediates DNA binding. Several alternative splice variants of TCF-1 have been identified, including TCF-1A, which share a conserved amino terminus and differ in the carboxy terminal sequences. The Wnt mediated signaling pathway induces cytosolic ∫-catenin binding to TCF proteins within the nucleus, leading to the enhanced expression of the Wnt target genes. The ∫-catenin-TCF complexes are negatively regulated by the adenomatous polyposis coli (APC) tumor suppressor protein, which phosphorylates b-catenin and, in turn, increases the degradation of cytosolic b-catenin and inhibits the transcriptional activity of the TCF proteins. Mutations in the APC gene, which are commonly observed in colorectal carcinomas, disrupt this regulatory pathway and correlate with an accumulation of ∫-catenin and the increased activation of the TCF target genes.
