Abstract
In C. elegans embryos, a Wnt/MAPK signaling pathway downregulates the TCF/LEF transcription factor POP-1, resulting in a lower nuclear level in signal-responsive cells compared to their sisters. Although the beta-catenin WRM-1 is required for POP-1 downregulation, a direct interaction between these two proteins does not seem to be required, as the beta-catenin-interacting domain of POP-1 is dispensable for both POP-1 downregulation and function in early embryos. We show here that WRM-1 downregulates POP-1 by promoting its phosphorylation by the MAP kinase LIT-1 and subsequent nuclear export via a 14-3-3 protein, PAR-5. In signal-responsive cells, we also detect a concurrent upregulation of nuclear LIT-1 that is dependent on Wnt/MAPK signaling. Our results suggest a model whereby Wnt/MAPK signaling downregulates POP-1 levels in responsive cells, in part by increasing nuclear LIT-1 levels, thereby increasing POP-1 phosphorylation and PAR-5-mediated nuclear export.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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14-3-3 Proteins
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Active Transport, Cell Nucleus / physiology
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Animals
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Caenorhabditis elegans / embryology
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Caenorhabditis elegans / enzymology*
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Cell Differentiation / physiology
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Cell Nucleus / metabolism
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Cytoskeletal Proteins / metabolism*
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism*
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Down-Regulation / physiology
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Embryo, Nonmammalian / cytology
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Embryo, Nonmammalian / embryology
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Embryo, Nonmammalian / enzymology
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High Mobility Group Proteins / genetics
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High Mobility Group Proteins / metabolism*
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MAP Kinase Signaling System / physiology
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Macromolecular Substances
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Membrane Proteins / metabolism
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Phosphorylation
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Protein Serine-Threonine Kinases
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Protein Structure, Tertiary / physiology
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Trans-Activators / metabolism*
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Tyrosine 3-Monooxygenase / metabolism*
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beta Catenin
Substances
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14-3-3 Proteins
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Caenorhabditis elegans Proteins
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Cytoskeletal Proteins
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DNA-Binding Proteins
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High Mobility Group Proteins
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Macromolecular Substances
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Membrane Proteins
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Trans-Activators
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WRM-1 protein, C elegans
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beta Catenin
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par-5 protein, C elegans
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pop-1 protein, C elegans
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Tyrosine 3-Monooxygenase
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Protein Serine-Threonine Kinases
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lit-1 protein, C elegans