WNT signaling controls many fundamental processes during animal development. WNT transduction is mediated by the association of beta-catenin with nuclear TCF DNA-binding factors.Lgs encodes the homolog of human BCL9, and the authors provided genetic and molecular evidence that these proteins exert their function by physically linking Pygo to beta-catenin. The PYGO1 and PYGO2 proteins, which contain 419 and 406 amino acids, respectively, possess a highly conserved PHD finger that interacts with homology domain-1 (HD1) of BCL9. The findings suggested that the recruitment of PYGO permits beta-catenin to transcriptionally activate WNT target genes and raised the possibility that a deregulation of these events may play a causal role in the development of B-cell malignancies.
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