title: Xrel3/XrelA attenuates β-catenin-mediated transcription during mesoderm formation in Xenopus embryos.
abstract: In Xenopus laevis embryonic development, activation of the Wnt/β-catenin pathway promotes mesoderm cell fate determination via Xnr (Xenopus nodal-related) expression. We have demonstrated previously that Rel/NF-κB (nuclear factor κB) proteins expressed in presumptive ectoderm limit the activity of Xnrs to the marginal zone of embryos during mesoderm induction, which assists to distinguish mesoderm from ectoderm. The mechanism of this regulation, however, is unknown. In the present study, we investigated whether Rel/NF-κB proteins are able to modulate mesoderm formation by mediating Wnt/β-catenin signalling. We determined that ectopic expression of XrelA or Xrel3 in the dorsal marginal zone perturbed dorsal mesoderm formation by down-regulating multiple Wnt/β-catenin target genes including Xnr3, Xnr5 and Xnr6. Ventral co-expression of XrelA or Xrel3 with either wild-type β-catenin or constitutively active β-cateninS37A abrogated β-catenin-induced axis duplication and attenuated β-catenin-stimulated reporter transcription. Lastly, we provide evidence that Xrel3, but not XrelA, can interact with β-catenin without affecting the association of β-catenin with other transcriptional co-activators in vitro. Both Xrel3 and XrelA, however, prevented the accumulation, in nuclei, of exogenously expressed and endogenous β-catenin in vivo. These results suggest that Rel proteins are able to bind β-catenin and attenuate β-catenin-mediated transcription by nuclear exclusion.
authors.affiliation: Terry Fox Cancer Research Laboratories, Division of Biomedical Sciences, Memorial University, 300 Prince Philip Drive, St John's, NL, Canada A1B 3V6.
authors.forename: Mark W L
authors.initials: MW
authors.lastname: Kennedy
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Kao
mesh_terms: D000818:Animals; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000378:metabolism*; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism*; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D055456:Nodal Signaling Ligands / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D051841:Transcription Factor RelB / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D029867:Xenopus Proteins / Q000235:genetics* / Q000378:metabolism*; D014982:Xenopus laevis / Q000196:embryology / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495266:CTNNB1 protein, Xenopus; D018398:Homeodomain Proteins; D016328:NF-kappa B; D055456:Nodal Signaling Ligands; D012333:RNA, Messenger; C112657:TP53 protein, Xenopus; D051996:Transcription Factor RelA; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin; C094620:nodal3.1 protein, Xenopus; C418882:nodal5 protein, Xenopus; C418883:nodal6 protein, Xenopus; C497596:relb protein, Xenopus; D051841:Transcription Factor RelB