A complex of Armadillo, Legless, and Pygopus coactivates dTCF to activate wingless target genes.
BACKGROUND
Upon receiving a Wnt signal, cells accumulate beta-catenin (Armadillo in Drosophila), which binds directly to TCF transcription factors, leading to the transcription of Wnt target genes. It is generally thought that beta-catenin/Armadillo is a transcriptional coactivator when bound to TCF in the nucleus and that this function is mediated by its C terminus. However, recent findings in Drosophila indicated that Armadillo may activate dTCF in the cytoplasm.


RESULTS
Here, I reexamine the mechanism of Armadillo's signaling function in light of Legless and Pygopus, two nuclear factors recently discovered to be essential for this function. I show that Armadillo, in order to activate dTCF, must enter the nucleus and form a complex with Legless and Pygopus. The ability of this complex to stimulate TCF-mediated transcription can be altered by linkage of a strong transcriptional activator or repressor to Armadillo. Furthermore, Armadillo is a strong transcriptional activator when fused to the yeast GAL4 DNA binding domain-an activity that depends on regions of the Armadillo repeat domain that mediate binding to Legless and to chromatin modifying and remodeling factors. Finally, linkage of the N-terminal region of Pygopus, but not the C terminus of Armadillo, to dominant-negative dTCF can restore its signaling activity in transgenic flies.


CONCLUSIONS
My evidence argues in favor of a revised coactivator factor model in which Armadillo's coactivator function depends on regions within its Armadillo repeat domain to which Legless/Pygopus and other transcriptional coactivators can bind. In contrast, the C terminus of Armadillo plays a less direct role in this function.
Thompson
Barry J
BJ
Division of Cell Biology, MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, United Kingdom.
D000818:Animals; D051186:Armadillo Domain Proteins; D002352:Carrier Proteins / Q000378:metabolism; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D008156:Luciferases; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014162:Transfection; D019076:Transgenes; D051155:Wnt1 Protein
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D002352:Carrier Proteins; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C453403:Lgs protein, Drosophila; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051155:Wnt1 Protein; C115159:pan protein, Drosophila; C453400:pygo protein, Drosophila; C074622:wg protein, Drosophila; D008156:Luciferases