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Regulation of TCF3 by Wnt-Dependent Phosphorylation during Vertebrate Axis Specification

Hikasa, Hiroki ; Ezan, Jerome ; Itoh, Keiji ; Li, Xiaotong ; Klymkowsky, Michael W. ; Sokol, Sergei Y.

Developmental cell, 2010-10, Vol.19 (4), p.521-532 [Periódico revisado por pares]

Cambridge, MA: Elsevier Inc

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Título:
Regulation of TCF3 by Wnt-Dependent Phosphorylation during Vertebrate Axis Specification
Autor: Hikasa, Hiroki ; Ezan, Jerome ; Itoh, Keiji ; Li, Xiaotong ; Klymkowsky, Michael W. ; Sokol, Sergei Y.
Assuntos: Amino Acid Sequence ; Animals ; beta Catenin - metabolism ; Binding Sites ; Biological and medical sciences ; Body Patterning - genetics ; Cell differentiation, maturation, development, hematopoiesis ; Cell physiology ; Conserved Sequence - genetics ; Embryo, Nonmammalian - cytology ; Embryo, Nonmammalian - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Expression Regulation, Developmental ; Humans ; Mice ; Molecular and cellular biology ; Molecular Sequence Data ; Phosphorylation ; Promoter Regions, Genetic - genetics ; Protein Binding ; Protein-Serine-Threonine Kinases - metabolism ; Repressor Proteins - metabolism ; Signal Transduction ; TCF Transcription Factors - antagonists & inhibitors ; TCF Transcription Factors - chemistry ; TCF Transcription Factors - genetics ; TCF Transcription Factors - metabolism ; Transcription Factor 7-Like 1 Protein ; Wnt Proteins - metabolism ; Xenopus - embryology ; Xenopus - genetics ; Xenopus - metabolism ; Xenopus Proteins - genetics ; Xenopus Proteins - metabolism
É parte de: Developmental cell, 2010-10, Vol.19 (4), p.521-532
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Descrição: A commonly accepted model of Wnt/β-catenin signaling involves target gene activation by a complex of β-catenin with a T-cell factor (TCF) family member. TCF3 is a transcriptional repressor that has been implicated in Wnt signaling and plays key roles in embryonic axis specification and stem cell differentiation. Here we demonstrate that Wnt proteins stimulate TCF3 phosphorylation in gastrulating Xenopus embryos and mammalian cells. This phosphorylation event involves β-catenin-mediated recruitment of homeodomain-interacting protein kinase 2 (HIPK2) to TCF3 and culminates in the dissociation of TCF3 from a target gene promoter. Mutated TCF3 proteins resistant to Wnt-dependent phosphorylation function as constitutive inhibitors of Wnt-mediated activation of Vent2 and Cdx4 during anteroposterior axis specification. These findings reveal an alternative in vivo mechanism of Wnt signaling that involves TCF3 phosphorylation and subsequent derepression of target genes and link this molecular event to a specific developmental process. ► Wnt proteins trigger phosphorylation of TCF3 and regulate its function in vivo ► HIPK2 plays a key role in TCF3 phosphorylation and anteroposterior patterning ► β-catenin functions as a scaffold for TCF3 phosphorylation ► Wnt target genes are activated by relief of TCF3-mediated transcriptional repression
Editor: Cambridge, MA: Elsevier Inc
Idioma: Inglês

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Regulation of TCF3 by Wnt-Dependent Phosphorylation during Vertebrate Axis Specification

Hikasa, Hiroki ; Ezan, Jerome ; Itoh, Keiji ; Li, Xiaotong ; Klymkowsky, Michael W. ; Sokol, Sergei Y.

Cambridge, MA: Elsevier Inc

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