Wnt/wingless signaling requires BCL9/legless-mediated recruitment of pygopus to the nuclear beta-catenin-TCF complex.
Wnt/Wingless signaling controls many fundamental processes during animal development. Wnt transduction is mediated by the association of beta-catenin with nuclear TCF DNA binding factors. Here we report the identification of two segment polarity genes in Drosophila, legless (lgs), and pygopus (pygo), and we show that their products are required for Wnt signal transduction at the level of nuclear beta-catenin. Lgs encodes the homolog of human BCL9, and we provide genetic and molecular evidence that these proteins exert their function by physically linking Pygo to beta-catenin. Our results suggest that the recruitment of Pygo permits beta-catenin to transcriptionally activate Wnt target genes and raise the possibility that a deregulation of these events may play a causal role in the development of B cell malignancies.
Kramps
Thomas
T
Institut für Molekularbiologie, Universität Zürich, Winterthurerstrasse 190, CH-8057, Zürich, Switzerland.
Peter
Oliver
O
Brunner
Erich
E
Nellen
Denise
D
Froesch
Barbara
B
Chatterjee
Sandipan
S
Murone
Maximilien
M
Züllig
Stephanie
S
Basler
Konrad
K
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051186:Armadillo Domain Proteins; D019521:Body Patterning / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics* / Q000302:isolation & purification; D002467:Cell Nucleus / Q000235:genetics* / Q000378:metabolism; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000302:isolation & purification; D004331:Drosophila melanogaster / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D005260:Female; D005820:Genetic Testing; D006609:High Mobility Group Proteins / Q000235:genetics*; D019476:Insect Proteins / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins; D046911:Macromolecular Substances; D008297:Male; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics*; D017434:Protein Structure, Tertiary / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
C495305:ARM protein, Drosophila; D048868:Adaptor Proteins, Signal Transducing; D051186:Armadillo Domain Proteins; C111180:BCL9 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D006609:High Mobility Group Proteins; D019476:Insect Proteins; D047908:Intracellular Signaling Peptides and Proteins; C453403:Lgs protein, Drosophila; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; C453402:PYGO1 protein, human; C453401:PYGO2 protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin; C115159:pan protein, Drosophila; C453400:pygo protein, Drosophila; C074622:wg protein, Drosophila