beta-TrCP is a negative regulator of Wnt/beta-catenin signaling pathway and dorsal axis formation in Xenopus embryos.
The Wnt/beta-catenin signaling pathway is responsible for the establishment of dorsoventral axis of Xenopus embryos. The recent finding of the F-box/WD40-repeat protein slimb in Drosophila, whose loss-of-function mutation causes ectopic activation of wingless signaling (Jiang, J., Struhl, G., 1998. Nature 391, 493-496), led us to examine the role of its vertebrate homolog betaTrCp in the Wnt/beta-catenin signaling and dorsal axis formation in Xenopus embryos. Co-injection of betaTrCp mRNA diminished Xwnt8 mRNA-induced axis formation and expression of Siamois and Xnr3, suggesting that betaTrCP is a negative regulator of the Wnt/beta-catenin signaling pathway. An mRNA for a betaTrCp mutant construct (DeltaF), which lacked the F-box domain, induced an ectopic axis and expression of Siamois and Xnr3. Because this activity of DeltaF was suppressed by co-injection of DeltaF TrCP mRNA, DeltaF likely acts in a dominant negative fashion. The activity of DeltaF was diminished by C-cadherin, glycogen synthase kinase 3 and Axin, but not by a dominant negative dishevelled. These results suggest that betaTrCp can act as a negative regulator of dorsal axis formation in Xenopus embryos.
Department of Zoology, University of Toronto, 25 Harbord Street, Toronto, Ontario M5S 3G5, Canada.
Y
Y
Marikawa
R P
RP
Elinson
D000818:Animals; D001665:Binding Sites / Q000235:genetics; D019521:Body Patterning / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000502:physiology*; D004625:Embryo, Nonmammalian / Q000502:physiology; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D017384:Sequence Deletion; D015398:Signal Transduction; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D014981:Xenopus / Q000196:embryology* / Q000502:physiology; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins
C471646:BTRC protein, Xenopus; C495266:CTNNB1 protein, Xenopus; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D011518:Proto-Oncogene Proteins; D018125:Receptors, Transforming Growth Factor beta; C093133:SIA1 protein, Xenopus; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins; C094620:nodal3.1 protein, Xenopus; D019204:GTP-Binding Proteins