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Nuclear Dvl, c-Jun, beta-catenin, and TCF form a complex leading to stabilization of beta-catenin-TCF interaction.
Gan, Xiao-qing; Wang, Ji-yong; Xi, Ying; Wu, Zhi-li; Li, Yi-ping; Li, Lin.
Afiliação
  • Gan XQ; State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
J Cell Biol ; 180(6): 1087-100, 2008 Mar 24.
Article em En | MEDLINE | ID: mdl-18347071
ABSTRACT
In canonical Wnt signaling, Dishevelled (Dvl) is a critical cytoplasmic regulator that releases beta-catenin from degradation. Here, we find that Dvl and c-Jun form a complex with beta-catenin-T-cell factor 4 (TCF-4) on the promoter of Wnt target genes and regulate gene transcription. The complex forms via two interactions of nuclear Dvl with c-Jun and beta-catenin, respectively, both of which bind to TCF. Disrupting the interaction of Dvl with either c-Jun or beta-catenin suppresses canonical Wnt signaling-stimulated transcription, and the reduction of Dvl diminished beta-catenin-TCF-4 association on Wnt target gene promoters in vivo. Expression of a TCF-Dvl fusion protein largely rescued the c-Jun knockdown Wnt signaling deficiency in mammalian cells and zebrafish. Thus, we confirm that c-Jun functions in canonical Wnt signaling and show that c-Jun functions as a scaffold in the beta-catenin-TCFs transcription complex bridging Dvl to TCF. Our results reveal a mechanism by which nuclear Dvl cooperates with c-Jun to regulate gene transcription stimulated by the canonical Wnt signaling pathway.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fosfoproteínas / Núcleo Celular / Proteínas Proto-Oncogênicas c-jun / Proteínas Adaptadoras de Transdução de Sinal / Proteínas Wnt / Beta Catenina / Fatores de Transcrição TCF Limite: Animals / Humans Idioma: En Revista: J Cell Biol Ano de publicação: 2008 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fosfoproteínas / Núcleo Celular / Proteínas Proto-Oncogênicas c-jun / Proteínas Adaptadoras de Transdução de Sinal / Proteínas Wnt / Beta Catenina / Fatores de Transcrição TCF Limite: Animals / Humans Idioma: En Revista: J Cell Biol Ano de publicação: 2008 Tipo de documento: Article País de afiliação: China