C. elegans TCF protein, POP-1, converts from repressor to activator as a result of Wnt-induced lowering of nuclear levels.
Canonical Wnt signaling converts the TCF/LEF transcription factor from repressor to activator by increasing nuclear levels of its coactivator, beta-catenin. A striking exception had been reported for Wnt-induced endoderm formation during C. elegans embryogenesis. It has long been believed that transcriptional activation of Wnt target genes in the endoderm precursor occurred due to a lowering of nuclear levels of the worm TCF/LEF protein, POP-1, effectively alleviating POP-1 repressive activity. Contrary to this model, we demonstrate here that POP-1 directly activates Wnt target genes in the endoderm precursor. Wnt converts POP-1 from a repressor to an activator, and this conversion requires that POP-1 nuclear levels be lowered in the endoderm precursor. We propose that the balance between TCF/LEF and coactivator(s), achieved by elevating coactivator levels (the canonical pathway) and/or reducing TCF/LEF levels (worm endoderm), determines Wnt signal strength.
Shetty
Premnath
P
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
Lo
Miao-Chia
MC
Robertson
Scott M
SM
Lin
Rueyling
R
D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004707:Endoderm / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D005819:Genetic Markers / Q000235:genetics; D006609:High Mobility Group Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D051153:Wnt Proteins / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D006609:High Mobility Group Proteins; D051153:Wnt Proteins; C096787:pop-1 protein, C elegans