MODULATION OF TRANSCRIPTIONAL REGULATION BY LEF-1 IN RESPONSE TO WNT-1 SIGNALING AND ASSOCIATION WITH BETA-CATENIN

Wnt signaling is thought to be mediated via interactions between beta- catenin and members of the LEF-1/TCF family of transcription factors. Here we study the mechanism of transcriptional regulation by LEF-1 in response to a Wnt-1 signal under conditions of endogenous beta-catenin in NIH 3T3 cells, and we examine whether association with beta-cateni n is obligatory for the function of LEF-1. We find that Wnt-1 signalin g confers transcriptional activation potential upon LEF-1 by associati on with beta-catenin in the nucleus. By mutagenesis, we identified spe cific residues in LEF-1 important for interaction with beta-catenin, a nd we delineated two transcriptional activation domains in beta-cateni n whose function is augmented in specific association with LEF-1. Fina lly, we show that a Wnt-1 signal and beta-catenin association are not required for the architectural function of LEF-1 in the regulation of the T-cell receptor alpha enhancer, which involves association of LEF- 1 with a different cofactor, ALY. Thus, LEF-1 can assume diverse regul atory functions by association with different proteins.