The zinc finger protein schnurri acts as a Smad partner in mediating the transcriptional response to decapentaplegic.

Dai, H; Hogan, C; Gopalakrishnan, B; Torres-Vazquez, J; Nguyen, M; Park, S; Raftery, L A; Warrior, R; Arora, K

Dai, H; Hogan, C; Gopalakrishnan, B; Torres-Vazquez, J; Nguyen, M; Park, S; Raftery, L A; Warrior, R; Arora, K.

Afiliación

Dai H; Program in Molecular Biology, MC1340, Department of Biological Sciences, University of Southern California, Los Angeles, California, 90089, USA.

Dev Biol ; 227(2): 373-87, 2000 Nov 15.

Article en En | MEDLINE | ID: mdl-11071761

RESUMEN

In Drosophila, a BMP-related ligand Decapentaplegic (Dpp) is essential for cell fate specification during embryogenesis and in imaginal disc development. Dpp signaling culminates in the phosphorylation and nuclear translocation of Mothers against dpp (Mad), a receptor-specific Smad that can bind DNA and regulate the transcription of Dpp-responsive genes. Genetic analysis has implicated Schnurri (Shn), a zinc finger protein that shares homology with mammalian transcription factors, in the Dpp signal transduction pathway. However, a direct role for Shn in regulating the transcriptional response to Dpp has not been demonstrated. In this study we show that Shn acts as a DNA-binding Mad cofactor in the nuclear response to Dpp. Shn can bind DNA in a sequence-specific manner and recognizes sites within a well-characterized Dpp-responsive promoter element, the B enhancer of the Ultrabithorax (Ubx) gene. The Shn-binding sites are relevant for in vivo expression, since mutations in these sites affect the ability of the enhancer to respond to Dpp. Furthermore we find that Shn and Mad can interact directly through discrete domains. To examine the relative contribution of the two proteins in the regulation of endogenous Dpp target genes we developed a cell culture assay and show that Shn and Mad act synergistically to induce transcription. Our results suggest that cooperative interactions between these two transcription factors could play an important role in the regulation of Dpp target genes. This is the first evidence that Dpp/BMP signaling in flies requires the direct interaction of Mad with a partner transcription factor.

Asunto(s)

Proteínas de Unión al ADN/metabolismo; Proteínas de Drosophila; Drosophila/metabolismo; Proteínas de Homeodominio/metabolismo; Proteínas de Insectos/metabolismo; Factores de Transcripción/metabolismo; Animales; Animales Modificados Genéticamente; Secuencia de Bases; Sitios de Unión/genética; Células COS; Células Cultivadas; ADN/genética; ADN/metabolismo; Cartilla de ADN/genética; Proteínas de Unión al ADN/genética; Sistema Digestivo/embriología; Sistema Digestivo/metabolismo; Drosophila/embriología; Drosophila/genética; Elementos de Facilitación Genéticos; Genes de Insecto; Proteínas de Homeodominio/genética; Proteínas de Insectos/genética; Factores de Transcripción/genética; Activación Transcripcional; Técnicas del Sistema de Dos Híbridos; Dedos de Zinc

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas de Homeodominio / Proteínas de Insectos / Proteínas de Drosophila / Proteínas de Unión al ADN / Drosophila Límite: Animals Idioma: En Revista: Dev Biol Año: 2000 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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