Phosphorylation by the beta-catenin/MAPK complex promotes 14-3-3-mediated nuclear export of TCF/POP-1 in signal-responsive cells in C. elegans.
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.
Lo
Miao-Chia
MC
Department of Molecular Biology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390, USA.
Gay
Frédérique
F
Odom
Raanan
R
Shi
Yang
Y
Lin
Rueyling
R
D048948:14-3-3 Proteins; D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000201:enzymology; D006609:High Mobility Group Proteins / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D046911:Macromolecular Substances; D008565:Membrane Proteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases; D017434:Protein Structure, Tertiary / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D051176:beta Catenin
D048948:14-3-3 Proteins; D029742:Caenorhabditis elegans Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D015534:Trans-Activators; C120104:WRM-1 protein, C elegans; D051176:beta Catenin; C106207:par-5 protein, C elegans; C096787:pop-1 protein, C elegans; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; C120085:lit-1 protein, C elegans