Pascual, Justine, Jacobs, Jelle, Sansores-Garcia, Leticia, Natarajan, Malini, Zeitlinger, Julia, Aerts, Stein, Halder, Georg and Hamaratoglu, Fisun ![]() ![]() |
Preview |
PDF
- Accepted Post-Print Version
Download (25MB) | Preview |
Abstract
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.
Item Type: | Article |
---|---|
Date Type: | Publication |
Status: | Published |
Schools: | Biosciences |
Publisher: | Elsevier (Cell Press) |
ISSN: | 1534-5807 |
Date of First Compliant Deposit: | 2 January 2019 |
Date of Acceptance: | 17 August 2017 |
Last Modified: | 17 Nov 2024 12:30 |
URI: | https://orca.cardiff.ac.uk/id/eprint/118010 |
Citation Data
Cited 26 times in Scopus. View in Scopus. Powered By Scopus® Data
Actions (repository staff only)
![]() |
Edit Item |