Abstract
Wnt growth factors mediate cell fate determination during embryogenesis and in the renewal of tissues in the adult. Wnts act by stabilizing cellular levels of the transcriptional coactivator beta-catenin, which forms complexes with sequence-specific DNA-binding Tcf/Lef transcription factors. In the absence of nuclear beta-catenin, Tcf/Lefs act as transcriptional repressors by binding to Groucho/TLE proteins. The molecular basis of the switch from transcriptional repression to activation during Wnt signaling has not been clear, in particular whether factors other than beta-catenin are required to disrupt the interaction between Groucho/TLE and Tcf/Lef. Using highly purified proteins, we demonstrate that beta-catenin displaces Groucho/TLE from Tcf/Lef by binding to a previously unidentified second, low-affinity binding site on Lef-1 that includes sequences just N-terminal to the DNA-binding domain, and that overlaps the Groucho/TLE-binding site.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Co-Repressor Proteins
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism*
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DNA / metabolism
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Humans
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Intercellular Signaling Peptides and Proteins / metabolism*
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Lymphoid Enhancer-Binding Factor 1
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Mice
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Protein Binding
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Repressor Proteins / genetics
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Repressor Proteins / metabolism*
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Trans-Activators / genetics
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Trans-Activators / metabolism*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation / genetics*
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Wnt Proteins
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beta Catenin
Substances
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CTNNB1 protein, human
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CTNNB1 protein, mouse
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Co-Repressor Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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Intercellular Signaling Peptides and Proteins
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LEF1 protein, human
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Lef1 protein, mouse
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Lymphoid Enhancer-Binding Factor 1
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Peptide Fragments
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Repressor Proteins
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TLE1 protein, human
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Tle1 protein, mouse
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Trans-Activators
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Transcription Factors
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Wnt Proteins
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beta Catenin
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DNA