Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Hippo reprograms the transcriptional response to Ras signalling

ABSTRACT: Mutations that lead to hyperactivation of Ras signaling are hallmarks of carcinomas. During development, signaling via Ras mediates cell fate decisions and cellular differentiation without causing hyper-proliferation. What determines whether Ras activation leads to differentiation or proliferation remains unknown. Here we show that the Hippo pathway reprograms the cellular response to Ras signaling in Drosophila. While hyperactivation of Ras signaling alone promotes cellular differentiation, additional loss of Hippo signaling drives aggressive hyper-proliferation. Transcriptome analysis combined with ChIP-nexus confirmed that the magnitude and specificity of Ras target gene expression strongly depends on the activity status of the Hippo pathway. This is because Hippo signaling directly regulates the expression of two key downstream transcription factors of the Ras pathway: the ETS-domain transcription factor Pointed and the transcriptional 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.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE96868 | GEO | 2017/09/26

SECONDARY ACCESSION(S): PRJNA379962

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Hippo Signaling Regulates Differentiation and Maintenance in the Exocrine Pancreas

Project description:The Hippo signaling pathway has become recognized as a context-dependent regulator of cell proliferation, differentiation, and apoptosis in species ranging from Drosophila to human. In this study, we sought to understand whether Hippo signaling plays a role in pancreatic development and organ homeostasis. We analyzed mRNA from 5 samples each from control and DKO mouse pancreas using Affymetrix MouseGene 1.0 ST Array platfrom. Array data was processed by Affymetrix array computational tools.

2013-02-14 | E-GEOD-44298 | biostudies-arrayexpress

OTUB1 promotes gastric cancer proliferation through regulating Hippo signaling pathway

Project description:OTUB1 promotes gastric cancer proliferation through regulating Hippo signaling pathway

| PRJNA809044 | ENA

Hippo Signaling Regulates Differentiation and Maintenance in the Exocrine Pancreas

2013-02-14 | GSE44298 | GEO

SDMA-shotgun analysis in pancreatic cancer cell lines

Project description:As a classic tumor suppressor pathway, Hippo signaling axis is activated by various extra-pathway factors to regulate cell differentiation and organ development. However, recent studies have reported that the activation of Hippo signaling pathway may be more dependent on the autophosphorylation of its core kinase cassette. Here, we demonstrate that protein arginine methyltransferase 5 (PRMT5) is involved in inducing the inactivation of Hippo signaling pathway in pancreatic cancer. Our study shows that the initiator serine/threonine kinase 3 (STK3, also known as MST2) of Hippo signaling pathway can be symmetrically di-methylated at arginine-461 (R461) and arginine-467 (R467) in the SARAH domain by PRMT5, and the methylated MST2 suppresses its autophosphorylation and kinase activity by blocking the formation of homodimer, thereby inactivating Hippo signaling pathway in pancreatic cancer. Moreover, we also discover that the specific PRMT5 inhibitor GSK3326595 re-activates the dysregulated Hippo signaling pathway

2023-08-18 | PXD044671 |

Transcription profiling of C. elegans with activated let-60 Ras

Project description:In Caenorhabditis elegans, let-60 Ras controls many cellular processes, such as differentiation of vulval epithelial cells, function of chemosensory neurons, and meiotic progression in the germ line. Although much is known about the let-60 Ras signaling pathway, relatively little is understood about the target genes induced by let-60 Ras signaling that carry out terminal effector functions leading to morphological change. We have used DNA microarrays to identify 708 genes that change expression in response to activated let-60 Ras.

2005-07-13 | E-SMDB-1398 | biostudies-arrayexpress

Transcriptional targets of Hippo signaling in mammalian cells

Project description:The Hippo pathway is an emerging signaling cascade involved in the regulation of organ size control. It consists of evolutionally conserved protein kinases that are sequentially phosphorylated and activated. The active Hippo pathway subsequently phosphorylates a transcription coactivator, YAP, which precludes its nuclear localization and transcriptional activation. Identification of transcriptional targets of YAP in diverse cellular contexts is therefore critical to the understanding of the molecular mechanisms in which the Hippo pathway restricts tissue growth. We used microarrays to profile the gene expression patterns upon acute siRNA knockdown of Hippo pathway components in multiple mammalian cell lines and identified a set of genes representing immediate transcriptional targets of the Hippo/Yap signaling pathway. Three mammalian cell lines (HEK293T, HepG2, HaCaT) were transfected with scramble siRNA controls or siRNAs against NF2 and LATS2, two core components of the Hippo pathway, simultaneously. Total RNAs were harvested four days after transfection to reveal the gene expression pattern unsing microarry. YAP and TAZ siRNAs were also transfected along with NF2 and LATS2 siRNAs to identify YAP/TAZ-dependent transcriptional targets upon loss of NF2/LATS2.

2013-12-31 | E-GEOD-49384 | biostudies-arrayexpress

Yap reprograms glutamine metabolism to increase nucleotide biosynthesis and enable liver growth

Project description:The Hippo pathway is an important regulator of organ size and tumorigenesis. It is unclear, however, how Hippo signaling provides the cellular building blocks required for rapid growth. Here, we report that transgenic zebrafish expressing an activated form of the Hippo pathway effector Yap1 develop enlarged livers and are prone to liver tumor formation. Transcriptomic profiling reveals that Yap1 reprograms genes involved in glutamine metabolism. Analysis of gene expression in WT and lf:Yap transgenic zebrafish livers.

2016-08-02 | E-GEOD-82246 | biostudies-arrayexpress

Downstream targets of let-60 Ras in Caenorhabditis elegans

2005-07-22 | E-GEOD-2974 | biostudies-arrayexpress

Gene expression data from livers of Yap+/+ and Yap+/- mice at postnatal day 30

Project description:Liver undergoes both size increase and differentiation during postnatal period, which in mice is approximately first 30 days. The mechanisms of simultaneous postnatal liver cell proliferation and maturation are not clear. In these experiments, role of yes associated protein (Yap), the downstream effector of Hippo Kinase signaling pathway was investigated. Total RNA isolated from livers of Yap+/+ and Yap+/- mice at Postnatal day 30. Pooled livers from 5 mice per genotype were used.

2012-04-04 | E-GEOD-31281 | biostudies-arrayexpress

Oncogenic RAS primes primary acute myeloid leukemia blasts for differentiation

Project description:RAS mutations are frequently found among AML patients, generating a constitutively active signaling protein changing cellular proliferation, differentiation and apoptosis. We previously showed that treatment of AML patients with high-dose cytarabine (HDAC) is preferentially beneficial for those with an oncogenic RAS mutation. By applying a murine AML model, we could ascribe this effect to a RAS-driven, p53-dependent induction of differentiation. Here, we sought to confirm the correlation between RAS status and differentiation of blasts obtained from AML patients. The expression signature of primary AML blasts expressing oncogenic RAS where compared to blasts with wtRAS. Blasts where obtained from peripheral blood or bone marrow samples from patients with CBFbeta-MYH11 translocations and with or without an additional NRAS point mutation. As a reference, the Kasumi-1 acute myeloid leukemia cell line was used.

2015-11-20 | E-MTAB-2090 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data