Wnt-3A/beta-catenin signaling induces transcription from the LEF-1 promoter

Mohammed Filali; Ningli Cheng; Duane Abbott; Vladimir Leontiev; John F Engelhardt

doi:10.1074/jbc.M107977200

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Wnt-3A/beta-catenin signaling induces transcription from the LEF-1 promoter

Journal article

Open access

Peer reviewed

Wnt-3A/beta-catenin signaling induces transcription from the LEF-1 promoter

Mohammed Filali, Ningli Cheng, Duane Abbott, Vladimir Leontiev and John F Engelhardt

The Journal of biological chemistry, Vol.277(36), pp.33398-33410

09/06/2002

DOI: 10.1074/jbc.M107977200

PMID: 12052822

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Abstract

Members of the Wnt family of secreted molecules have been established as key factors in determining cell fate and morphogenic signaling. It has long been recognized that Wnt induces morphogenic signaling through the Tcf/LEF-1 cascade by regulating free intracellular levels of beta-catenin, a co-factor for Tcf/LEF-1 transcription factors. In the present study, we have demonstrated that Wnt-3A can also directly induce transcription from the LEF-1 promoter. This induction was dependent on glycogen synthase kinase 3beta inactivation, a rise in free intracellular beta-catenin, and a short 110-bp Wnt-responsive element (WRE) in the LEF-1 promoter. Linear and internal deletion of this WRE led to a dramatic increase in constitutive LEF-1 promoter activity and loss of Wnt-3A responsiveness. In isolation, the 110-bp WRE conferred context-independent Wnt-3A or beta-catenin(S37A) responsiveness to a heterologous SV40 promoter. Studies expressing dominant active and negative forms of LEF-1, beta-catenin, GSK-3beta, and beta-catenin/LEF-1 fusions suggest that Wnt-3A activates the LEF-1 promoter through a beta-catenin-dependent and LEF-1-independent process. Wnt-3A expression also induced multiple changes in the binding of factors to the WRE and suggests that regulatory mechanisms may involve modulation of a multiprotein complex. In summary, these results provide evidence for transcriptional regulation of the LEF-1 promoter by Wnt and enhance the mechanistic understanding of Wnt/beta-catenin signaling in the regulation of LEF-1-dependent developmental processes.

Transfection

Signal Transduction

Luciferases - metabolism

Humans

Transcriptional Activation

Molecular Sequence Data

Wnt Proteins

RNA, Messenger - metabolism

Lymphoid Enhancer-Binding Factor 1

Base Sequence

Cytoskeletal Proteins - metabolism

Transcription, Genetic

Binding Sites

Genes, Reporter

Cell Line

Promoter Regions, Genetic

Gene Library

beta Catenin

Transcription Factors - biosynthesis

Transcription Factors - genetics

DNA-Binding Proteins - genetics

Plasmids - metabolism

Proteins - metabolism

Trans-Activators - metabolism

Wnt3 Protein

Models, Genetic

Wnt3A Protein

DNA, Complementary - metabolism

DNA-Binding Proteins - biosynthesis

Details

Title: Subtitle: Wnt-3A/beta-catenin signaling induces transcription from the LEF-1 promoter
Creators: Mohammed Filali - Department of Anatomy and Cell Biology and the Department of Internal Medicine, University of Iowa, Iowa City, Iowa 52242, USA
Ningli Cheng
Duane Abbott
Vladimir Leontiev
John F Engelhardt
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.277(36), pp.33398-33410
DOI: 10.1074/jbc.M107977200
PMID: 12052822
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: United States
Grant note: R01 DK047967 / NIDDK NIH HHS R01 DK47967 / NIDDK NIH HHS
Language: English
Date published: 09/06/2002
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Anatomy and Cell Biology; Radiation Oncology; Internal Medicine
Record Identifier: 9984025476202771

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