Your browser doesn't support javascript.
loading
The tumor suppressor Brat controls neuronal stem cell lineages by inhibiting Deadpan and Zelda.
Reichardt, Ilka; Bonnay, François; Steinmann, Victoria; Loedige, Inga; Burkard, Thomas R; Meister, Gunter; Knoblich, Juergen A.
Afiliación
  • Reichardt I; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
  • Bonnay F; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
  • Steinmann V; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
  • Loedige I; Laboratory for RNA Biology, Biochemistry Center Regensburg (BZR), University of Regensburg, Regensburg, Germany.
  • Burkard TR; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria.
  • Meister G; Laboratory for RNA Biology, Biochemistry Center Regensburg (BZR), University of Regensburg, Regensburg, Germany.
  • Knoblich JA; Institute of Molecular Biotechnology of the Austrian Academy of Sciences (IMBA), Vienna, Austria juergen.knoblich@imba.oeaw.ac.at.
EMBO Rep ; 19(1): 102-117, 2018 01.
Article en En | MEDLINE | ID: mdl-29191977
The TRIM-NHL protein Brain tumor (Brat) acts as a tumor suppressor in the Drosophila brain, but how it suppresses tumor formation is not completely understood. Here, we combine temperature-controlled brat RNAi with transcriptome analysis to identify the immediate Brat targets in Drosophila neuroblasts. Besides the known target Deadpan (Dpn), our experiments identify the transcription factor Zelda (Zld) as a critical target of Brat. Our data show that Zld is expressed in neuroblasts and required to allow re-expression of Dpn in transit-amplifying intermediate neural progenitors. Upon neuroblast division, Brat is enriched in one daughter cell where its NHL domain directly binds to specific motifs in the 3'UTR of dpn and zld mRNA to mediate their degradation. In brat mutants, both Dpn and Zld continue to be expressed, but inhibition of either transcription factor prevents tumorigenesis. Our genetic and biochemical data indicate that Dpn inhibition requires higher Brat levels than Zld inhibition and suggest a model where stepwise post-transcriptional inhibition of distinct factors ensures sequential generation of fates in a stem cell lineage.
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Nucleares / Linaje de la Célula / Proteínas de Drosophila / Proteínas de Unión al ADN / Drosophila melanogaster / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico / Células-Madre Neurales / Carcinogénesis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Proteínas Nucleares / Linaje de la Célula / Proteínas de Drosophila / Proteínas de Unión al ADN / Drosophila melanogaster / Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico / Células-Madre Neurales / Carcinogénesis Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: EMBO Rep Asunto de la revista: BIOLOGIA MOLECULAR Año: 2018 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Reino Unido