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Phosphorylation by the β-Catenin/MAPK Complex Promotes 14-3-3-Mediated Nuclear Export of TCF/POP-1 in Signal-Responsive Cells in C. elegans
Open accessAbstract
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.
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“In C. elegans, the phosphorylation sites in POP-1 by LIT-1 were identified and these sites did not correspond to the target sites in LEF1 by NLK.16)”
From Mammalian Nemo-like kinase enhances .BETA.-catenin-TCF transcription activity in human osteosarcoma and neuroblastoma cells (2007) · cites this paper as [16]
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Metadata
- Authors
- Lo, M.-C., Gay, F., Odom, R., Shi, Y., & Lin, R.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Harvard University (US)
- Corresponding author
- Lin, Rueyling
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 117
- Issue
- 1
- Pages
- 95-106
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2157756800
- Cited by
- 138
- References
- 38
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 3 · 2019: 1 · 2018: 4 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 9
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (HD37933)
- March of Dimes Foundation (GM58012, FY01-265)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › 14-3-3 protein interactions
- Keywords
- β-catenin, POP-1, TCF/LEF transcription factors, 14-3-3 proteins, protein phosphorylation, nuclear export, Caenorhabditis elegans embryo, transcriptional downregulation
- MeSH terms
- Animals, Cell Differentiation, Cell Nucleus, Cytoskeletal Proteins, DNA-Binding Proteins, Embryo, Nonmammalian, High Mobility Group Proteins, Membrane Proteins, Phosphorylation, Tyrosine 3-Monooxygenase, Trans-Activators, Down-Regulation, Caenorhabditis elegans, Protein Serine-Threonine Kinases, Protein Structure, Tertiary, MAP Kinase Signaling System, Active Transport, Cell Nucleus, Caenorhabditis elegans Proteins, Macromolecular Substances, 14-3-3 Proteins, beta Catenin
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