Inhibition of Drosophila Wg signaling involves competition between Mad and Armadillo/beta-catenin for dTcf binding.
Precisely regulated signal transduction pathways are crucial for the regulation of developmental events and prevention of tumorigenesis. Both the Transforming Growth Factor beta (TGFbeta)/Bone morphogenetic protein (BMP) and Wnt/Wingless (Wg) pathways play essential roles in organismal patterning and growth, and their deregulation can lead to cancers. We describe a mechanism of interaction between Drosophila Wg and BMP signaling in which Wg target gene expression is antagonized by BMP signaling. In vivo, high levels of both an activated BMP receptor and the BMP effector Mad can inhibit the expression of Wg target genes. Conversely, loss of mad can induce Wg target gene expression. In addition, we find that ectopic expression in vivo of the Wg transcription factor dTcf is able to suppress the inhibitory effect caused by ectopic Mad. In vitro binding studies revealed competition for dTcf binding between Mad and the Wnt effector beta-catenin/Armadillo (Arm). Our in vivo genetic analyses and target gene studies support a mechanism consistent with the in vitro binding and competition studies, namely that BMP pathway components can repress Wg target gene expression by influencing the binding of Arm and dTcf.
Zeng
Yi Arial
YA
Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia, Canada.
Rahnama
Maryam
M
Wang
Simon
S
Lee
Wendy
W
Verheyen
Esther M
EM
D000818:Animals; D051186:Armadillo Domain Proteins / Q000378:metabolism; D001667:Binding, Competitive; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation; D018716:Molecular Mimicry; D046912:Multiprotein Complexes / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism; D014921:Wings, Animal / Q000166:cytology / Q000378:metabolism; D051155:Wnt1 Protein / Q000378:metabolism
C495305:ARM protein, Drosophila; D051186:Armadillo Domain Proteins; D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; D046912:Multiprotein Complexes; D012097:Repressor Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C064196:dpp protein, Drosophila; C115159:pan protein, Drosophila; C074622:wg protein, Drosophila