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

Cell. 2004 Apr 2;117(1):95-106. doi: 10.1016/s0092-8674(04)00203-x.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 14-3-3 Proteins
  • Active Transport, Cell Nucleus / physiology
  • Animals
  • Caenorhabditis elegans / embryology
  • Caenorhabditis elegans / enzymology*
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cell Differentiation / physiology
  • Cell Nucleus / metabolism
  • Cytoskeletal Proteins / metabolism*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / physiology
  • Embryo, Nonmammalian / cytology
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / enzymology
  • High Mobility Group Proteins / genetics
  • High Mobility Group Proteins / metabolism*
  • MAP Kinase Signaling System / physiology
  • Macromolecular Substances
  • Membrane Proteins / metabolism
  • Phosphorylation
  • Protein Structure, Tertiary / physiology
  • Protein-Serine-Threonine Kinases
  • Trans-Activators / metabolism*
  • Tyrosine 3-Monooxygenase / metabolism*
  • beta Catenin

Substances

  • 14-3-3 Proteins
  • Caenorhabditis elegans Proteins
  • Cytoskeletal Proteins
  • DNA-Binding Proteins
  • High Mobility Group Proteins
  • Macromolecular Substances
  • Membrane Proteins
  • Trans-Activators
  • WRM-1 protein, C elegans
  • beta Catenin
  • par-5 protein, C elegans
  • pop-1 protein, C elegans
  • Tyrosine 3-Monooxygenase
  • Protein-Serine-Threonine Kinases
  • lit-1 protein, C elegans