The retinal determination gene dachshund restricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex
| Autor: | Catarina Brás-Pereira, Fernando Casares, Florence Janody |
|---|---|
| Přispěvatelé: | Fundação para a Ciência e a Tecnologia (Portugal), Ministerio de Economía y Competitividad (España), European Commission, Ministerio de Ciencia e Innovación (España) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Homothorax
Dachshund Blotting Western Cyclin B Retina 03 medical and health sciences 0302 clinical medicine Animals Drosophila Proteins Drosophila eye development Nuclear protein Enhancer Yorkie Molecular Biology Transcription factor 030304 developmental biology Cell Proliferation Genetics Homeodomain Proteins 0303 health sciences Organ growth Decapentaplegic biology Nuclear Proteins YAP-Signaling Proteins Cell cycle Immunohistochemistry eye diseases Cell biology Imaginal disc biology.protein Trans-Activators Progenitor proliferation Drosophila 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | The Drosophila transcriptional co-activator protein Yorkie and its vertebrate orthologs YAP and TAZ are potent oncogenes, whose activity is normally kept in check by the upstream Hippo kinase module. Upon its translocation into the nucleus, Yorkie forms complexes with several tissue-specific DNA-binding partners, which help to define the tissue-specific target genes of Yorkie. In the progenitor cells of the eye imaginal disc, the DNA-binding transcription factor Homothorax is required for Yorkie-promoted proliferation and survival through regulation of the bantam microRNA (miRNA). The transit from proliferating progenitors to cell cycle quiescent precursors is associated with the progressive loss of Homothorax and gain of Dachshund, a nuclear protein related to the Sno/Ski family of co-repressors. We have identified Dachshund as an inhibitor of Homothorax-Yorkie-mediated cell proliferation. Loss of dachshund induces Yorkie-dependent tissue overgrowth. Conversely, overexpressing dachshund inhibits tissue growth, prevents Yorkie or Homothorax-mediated cell proliferation of disc epithelia and restricts the transcriptional activity of the Yorkie-Homothorax complex on the bantam enhancer in Drosophila cells. In addition, Dachshund collaborates with the Decapentaplegic receptor Thickveins to repress Homothorax and Cyclin B expression in quiescent precursors. The antagonistic roles of Homothorax and Dachshund in Yorkie activity, together with their mutual repression, ensure that progenitor and precursor cells are under distinct proliferation regimes. Based on the crucial role of the human dachshund homolog DACH1 in tumorigenesis, our work suggests that DACH1 might prevent cellular transformation by limiting the oncogenic activity of YAP and/or TAZ. This work was supported by grants from Fundação para a Ciência e Tecnologia [PTDC/BIA-BCM/71674/2006] to F.J.; and from the Spanish Ministry of Economy and Competitiveness (MINECO); and EU Feder Funds [BFU2012-34324] to F.C.; and Consolider ‘From Genes to Shape’ (MICINN) of which F.C. was a participant researcher. C.B.-P. was the recipient of fellowships from Fundação para a Ciência e Tecnologia [SFRH/BPD/46983/2008]. F.J. is the recipient of IF/01031/2012 from Fundação para a Ciência e Tecnologia. |
| Databáze: | OpenAIRE |
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