Modulation of Transcriptional Regulation by LEF-1 in Response to Wnt-1 Signaling and Association with β-Catenin
Year: 1998
Type: article
Abstract: 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-catenin is obligatory for the function of LEF-1. We find that Wnt-1 signaling confers transcriptional activation potential upon LEF-1 by association with beta-catenin in the nucleus. By mutagenesis, we identified specific residues in LEF-1 important for interaction with beta-catenin, and we delineated two transcriptional activation domains in beta-catenin whose function is augmented in specific association with LEF-1. Finally, 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 regulatory functions by association with different proteins.
Source: Molecular and Cellular Biology
Authors: Shu-Chi Hsu, Juan Galceran, Rudolf Grosschedl
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
Funder: Howard Hughes Medical Institute
OpenAlex ID: W2141175150