Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Deciphering the direct transcriptional targets of the Drosophila Activating transcription factor 3 (Atf3) via ChIp-seq: Atf3 bridges the gap between cell polarity and the nucleus

ABSTRACT: Epithelial structure and function are governed by evolutionarily conserved signaling programs. The Drosophila Activating transcription factor 3 (Atf3) prevents epithelial cell replacement during abdominal morphogenesis, yet its transcriptional targets are unknown. Here we demonstrate that Atf3 positively and negatively regulates target genes central to cytoskeleton dynamics and adhesion. Epithelial clones overexpressing Atf3 are enriched for basolateral proteins at the expense of apical identity. Strikingly, Atf3 functions downstream of the Scrib polarity module. Depleting either scrib or dlg1 induces atf3 expression, while loss of atf3 suppresses differentiation and polarity defects in cells deficient for the Scrib complex

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE71206 | GEO | 2018/02/20

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional response to Activating transcription factor 3 (Atf3) activity in the Drosophila eye antenna imaginal disc (EAD) epithelium.

Project description:Here we describe the transcriptional response to Atf3 expression in the EAD. Atf3 is a cell polarity response gene acting downstream of the membrane-associated Scribble polarity complex. Loss of the neoplastic tumor suppressors Scribble or Dlg1 induces Atf3 expression via aPKC signaling. Using ChIP-seq we have determined that Atf3 targets are enriched for roles in cytoarchitecture. Gain of Atf3 function interferes with organization of the microtubule network, thereby disturbing vesicular trafficking processes including endocytosis, and consequently alters the distribution of key polarity proteins along the apicobasal axis. Conversely, removal of Atf3 from cells lacking Dlg1 suppresses trafficking defects and restores both the normal localization of polarity determinants and epithelial differentiation. These results thus establish loss of polarity as a novel cue that induces Atf3 and demonstrate that gain of Atf3 function drives specific hallmarks of epithelial cells deficient for the Scribble polarity module.

2018-02-20 | GSE89845 | GEO

E-cadherin bridges cell polarity and spindle orientation to ensure prostate epithelial integrity and prevent carcinogenesis in vivo

Project description:Cell polarity and correct mitotic spindle positioning are essential for the maintenance of a proper prostate epithelial architecture, and disruption of the two biological features occurs at early stages in prostate tumorigenesis. However, whether and how these two epithelial attributes are connected in vivo is largely unknown. We herein report that conditional genetic deletion of E-cadherin, a key component of adherens junctions, in a mouse model results in loss of prostate luminal cell polarity and randomization of spindle orientations. Critically, E-cadherin ablation causes prostatic hyperplasia which progresses to invasive adenocarcinoma. Mechanistically, E-cadherin and the spindle positioning determinant LGN interacts with the PDZ domain of cell polarity protein SCRIB and form a ternary protein complex to bridge cell polarity and cell division orientation. These findings provide a novel mechanism by which E-cadherin acts an anchor to maintain prostate epithelial integrity and to prevent carcinogenesis in vivo.

2018-08-01 | GSE115204 | GEO

Mislocalization of the cell polarity protein Scribble (Scrib) induces SPARC secretion in hepatocellular carcinoma

Project description:Cell polarity is crucial for the maintenance of epithelial cell function and its loss may have an im-portant role in the development and progression of cancer. We here show that overexpression and cytoplasmic enrichment of the baso-lateral polarity complex protein Scribble (Scrib) correlates with poor prognosis of hepatocellular cancer (HCC) patients. Expression of the cytoplasmic ScribP305L in hepatocellular cells induces epithelial to mesenchymal transition (EMT) and supports HCC cell invasion in comparison to cells expressing membrane-localized ScribWT. ScribP305L induces AKT signalling through destabilization of the phosphatases phosphatase and tensin homolog (PTEN) and PH domain and leucine rich repeat protein phosphatase 1 (PHLPP1). Moreover, cytoplasmic ScribP305L stimulates the expression of secreted protein acidic and cysteine rich (SPARC) de-pending on the AP1 constituents ATF2 and JunB, which drives HCC cell invasiveness. In vivo, combined hydrodynamic delivery of ScribP305L but not ScribWT and c-MYC initiates tumour for-mation in hepatocytes and cytoplasmic Scrib correlates with AKT phosphorylation, and AP1 ex-pression in human HCC tissues. Together, overexpression and mislocalization of Scrib represents an early event involved in the initiation and progression of liver cancer.

2017-11-30 | GSE93742 | GEO

The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in development

Project description:Wingless (Wg)/Wnt signaling is conserved in all metazoan animals and plays critical roles in development. The Wg/Wnt morphogen reception is essential for signal activation, whose activity is mediated through the receptor complex and a scaffold protein Dishevelled (Dsh). We report here that the exon junction complex (EJC) activity is indispensable for Wg signaling by maintaining an appropriate level of Dsh protein for Wg ligand reception in Drosophila. Transcriptome analyses in Drosophila wing imaginal discs indicate that the EJC controls the splicing of the cell polarity gene disc large 1 (dlg1), whose coding protein directly interacts with Dsh. Genetic and biochemical experiments demonstrate that Dlg1 protein acts independently from its role in cell polarity to protect Dsh protein from lysosomal degradation. More importantly, human orthologous Dlg protein is sufficient to promote Dvl protein stabilization and Wnt signaling activity, thus revealing a conserved regulatory mechanism of Wg/Wnt signaling by Dlg and EJC. whole transcriptome RNA-seq to examine mRNAs extracted from wildtype (i.e. overexpressing lacZ) and pre-EJC-defective (i.e. overexpressing tsu RNAi) wing discs, respectively.

2016-08-19 | E-GEOD-81220 | biostudies-arrayexpress

A survival mechanism controlled by cadherins and Dlg1 polarity complex inhibits Fas cell death receptor signaling

Project description:A fine regulation of epithelia cell death is required to maintain tissue integrity and homeostasis. At a cellular level, this life and death decision is controlled by environmental stimuli including death receptors activation. Here, we show that establishment of cell polarity and AJ formation control the pro-apoptotic signaling emanating from the death receptor Fas. We demonstrate that in colon epithelia Fas concentrates at cell-cell junctions together with the E-cadherin, which protects cells from FasL-induced cell death. The Fas-cadherin association requires the C terminal PDZ binding site of Fas and, using a proteomic approach, we showed that this domain allows the association with the polarity molecule Dlg1. We proved that the interaction of Fas with this scaffold molecule participate to this cell death protection. Therefore inhibition of FasL-induced cell death by Fas-cadherin-Dlg1 complex is a double-edged sword mechanism that helps to maintain epithelial homeostasis by (i) protecting normal polarized epithelia from apoptosis (ii) promoting the elimination of compromised non-polarized cells.

2018-09-20 | PXD009659 | Pride

The exon junction complex regulates the splicing of cell polarity gene dlg1 to control Wingless signaling in development

2016-08-19 | GSE81220 | GEO

RNA-Seq of Notch-stimulated overgrowing Drosophila melanogaster wing imaginal discs

Project description:Aim: mRNA profile of larval wing imaginal discs of Drosophila melanogaster to study the cooperation between Notch activation and loss of epithelial polarity (scrib mutation) during neoplastic growth. Results: The combination of Notch activation and scribble mutation (NS) results in mRNA expression changes that, while partly overlapping with Notch only (N), and with scrib mutation only (S), are unique to the combination

2021-10-07 | GSE185339 | GEO

Su(H) ChIP-on-chip of Notch-stimulated overgrowing Drosophila melanogaster wing imaginal discs

Project description:Aim: Su(H) chromatin occupancy profiling by ChIP on larval wing imaginal discs of Drosophila melanogaster to study the cooperation between Notch activation and loss of epithelial polarity (scrib mutation) during neoplastic growth. Results: The combination of Notch activation and scribble mutation (NS) does not lead to a general redeployment of Su(H) binding as compared to individual conditions (Notch only (N), and scrib mutation only (S))

2021-10-08 | GSE185490 | GEO

The tumor suppressor SCRIB is a negative modulator of the Wnt/-catenin signaling (part 2)

Project description:Epithelial tissues are highly organized structures that rely on cell polarity pathways driven by membrane receptors and scaffolding proteins. SCRIBBLE is a cytoplasmic scaffold present at cell-cell junctions in polarized cells that contains LRR and PDZ domains. The current interactome of SCRIB and LRRC1 consists of 67 and 30 protein interaction partners respectively with only 9 (10%) common partners (BioGRID, version 3.5). Our study identified a protein complex associated to SCRIB stabilized by the inhibition of the proteasome and further characterize SCRIB act as negative modulator of the Wnt/β-catenin signaling.

2019-09-25 | PXD013636 | Pride

Identification of genes responsive to change in apical polarity in the breast epithelium

Project description:Differentiation of monolayered epithelia is characterized by the formation of a basoapical polarity axis, except during the early stages of cancer development. Using mammary glandular structures (acini) produced in a three-dimensional cell culture system we have demonstrated that, in order for mammary epithelial cells to exit quiescence and enter the cell cycle, acini have to lose apical polarity. In order to identify the genes dependent on apical polarity that could control cell quiescence, and possibly other aspects of tissue homeostasis, we have used Affymetrix technology microarray analysis of the 22,277 features/genes of the Human Genome U133A 2.0 array Chip in apically polarized and non-polarized breast epithelial acinar cells in three-dimensional culture. Genes commonly down-regulated in two treatments that altered apical polarity compared to control were considered to be dependent on apical polarity status for their transcription. Apically polarized (Control) and two different populations of non-polarized human mammary epithelial cells (18-alpha-glycyrrhetinic acid =AGA, and 5-aza-2'-deoxycytidine =Aza) were used for microarray analysis containing four biological replicates (1-4) for each treatment. The two treatments that cause loss of apical polarity were compared to reference apically polarized control samples using two different statistical analysis methods (FDR and HolmM-bM-^@M-^Ys).

2012-02-29 | E-GEOD-35165 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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