Cited by 143Wnt/β-catenin signaling in development and cancerDevelopmental Biology and Gene Regulation14-3-3 protein interactions

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

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Lo, Miao-Chia, Gay, Frédérique, Odom, Raanan, Shi, Yang, Lin, Rueyling·2004·Cell

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.

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Crossref · 10.1016/s0092-8674(04)00203-x

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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
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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