Modulation of transcriptional regulation by LEF-1 in response to Wnt-1 signaling and association with beta-catenin.

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.

journal_name

Mol Cell Biol

authors

Hsu SC,Galceran J,Grosschedl R

doi

10.1128/mcb.18.8.4807

subject

Has Abstract

pub_date

1998-08-01 00:00:00

pages

4807-18

issue

8

eissn

0270-7306

issn

1098-5549

journal_volume

18

pub_type

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