Maternal Wnt-β-Catenin Signaling Coactivates Transcription through NF-κB Binding Sites during Xenopus Axis FormationReportar como inadecuado




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Maternal Wnt-β-Catenin signaling establishes a program of dorsal-specific gene expression required for axial patterning in Xenopus. We previously reported that a subset of dorsally expressed genes depends not only on Wnt-β-Catenin stimulation, but also on a MyD88-dependent Toll-like receptor-IL1-receptor TLR-IL1-R signaling pathway. Here we show that these two signal transduction cascades converge in the nucleus to coactivate gene transcription in blastulae through a direct interaction between β-Catenin and NF-κB proteins. A transdominant inhibitor of NF-κB, ΔNIκBα, phenocopies loss of MyD88 protein function, implicating Rel-NF-κB proteins as selective activators of dorsal-specific gene expression. Sensitive axis formation assays in the embryo demonstrate that dorsalization by Wnt-β-Catenin requires NF-κB protein activity, and vice versa. Xenopus nodal-related 3 Xnr3 is one of the genes with dual β-Catenin-NF-κB input, and a proximal NF-κB consensus site contributes to the regional activity of its promoter. We demonstrate in vitro binding of Xenopus β-Catenin to several XRel proteins. This interaction is observed in vivo upon Wnt-stimulation. Finally, we show that a synthetic luciferase reporter gene responds to both endogenous and exogenous β-Catenin levels in an NF-κB motif dependent manner. These results suggest that β-Catenin acts as a transcriptional co-activator of NF-κB-dependent transcription in frog primary embryonic cells.



Autor: Neil J. Armstrong, François Fagotto, Christian Prothmann, Ralph A. W. Rupp

Fuente: http://plos.srce.hr/



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