Hippo Reprograms the Transcriptional Response to Ras Signaling
| Autor: | Malini Natarajan, Fisun Hamaratoglu, Leticia Sansores-Garcia, Julia Zeitlinger, Georg Halder, Justine Pascual, Stein Aerts, Jelle Jacobs |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Transcription Genetic Cellular differentiation Genes Insect Cell fate determination Biology Models Biological Regulon General Biochemistry Genetics and Molecular Biology Transcriptome 03 medical and health sciences Anti-apoptotic Ras signalling cascade Animals Drosophila Proteins Molecular Biology Transcription factor Cell Proliferation Hippo signaling pathway Sequence Analysis RNA Pupa Gene Expression Regulation Developmental Cell Differentiation Cell Biology Cell biology ErbB Receptors 030104 developmental biology Drosophila melanogaster Hippo signaling Mutation ras Proteins Signal transduction Developmental Biology Signal Transduction Transcription Factors |
| Zdroj: | Developmental cell. 42(6) |
| ISSN: | 1878-1551 1534-5807 |
| Popis: | Hyperactivating mutations in Ras signaling are hallmarks of carcinomas. Ras signaling mediates cell fate decisions as well as proliferation during development. It is not known what dictates whether Ras signaling drives differentiation versus proliferation. Here we show that the Hippo pathway is critical for this decision. Loss of Hippo switches Ras activation from promoting cellular differentiation to aggressive cellular proliferation. Transcriptome analysis combined with genetic tests show that this excessive proliferation depends on the synergistic induction of Ras target genes. Using ChIP-nexus, we find that Hippo signaling keeps Ras targets in check by directly regulating the expression of two key downstream transcription factors of Ras signaling: the ETS-domain transcription factor Pointed and the repressor Capicua. Our results highlight how independent signaling pathways can impinge on each other at the level of transcription factors, thereby providing a safety mechanism to keep proliferation in check under normal developmental conditions. |
| Databáze: | OpenAIRE |
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