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

ABSTRACT: 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.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE89845 | GEO | 2018/02/20

REPOSITORIES: GEO

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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

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Basolateral Protein Scribble Provides Phosphatase PP1 to a Signaling Network Maintaining Apicobasal Polarity

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2021-11-03 | PXD028919 | Pride

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2011-01-29 | E-GEOD-26241 | biostudies-arrayexpress

Microarray based gene expression comparison between wild type and yap-1(ys38) C. elegans embyos

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2024-04-21 | GSE263981 | GEO

Time-resolved function of cell polarity kinases PRKCZ and PRKCI in CNS myelination [bulk_oligo]

2024-04-21 | GSE263979 | GEO

CDC42 controlled apical-basal polarity regulates intestinal stem cell to transit amplifying cell fate transition via YAP-EGF-mTOR signaling

Project description:Epithelial polarity is controlled by a polarity machinery including the Rho GTPase CDC42 and Scribble/PAR. By using intestinal stem cell (ISC)-specific deletion of CDC42 in Olfm4-IRES-eGFPCreERT2;CDC42flox/flox mice, we found that ISC-initiated CDC42 loss caused a drastic hyper-proliferation of transit amplifying (TA) cells and disrupted epithelial polarity. CDC42-null crypts displayed expanded TA cell and diminished ISC populations, accompanied by elevated hippo signaling via YAP/TAZ - Ereg and mTOR activation, independent from canonical Wnt signaling. YAP/TAZ conditional knockout restored the balance of ISC/TA cell populations and crypt proliferation but did not rescue the polarity in CDC42-null small intestine. mTOR or EGFR inhibitor treatment of CDC42 KO mice exhibited similar rescuing effects without affecting YAP/TAZ signaling. Inducible ablation of Scribble in intestinal epithelial cells mimics that of CDC42 KO defects including crypt hyperplasia and hippo signaling activation. Mammalian epithelial polarity regulates ISC and TA cell fate and proliferation via a hippo-Ereg-mTOR cascade.

2021-10-23 | GSE166736 | GEO

aPKC controls endothelial growth by modulating c-Myc via FoxO1 DNA binding ability

Project description:Strict regulation of proliferation is vital for development, whereas unregulated cell proliferation is a fundamental characteristic of cancer. The polarity protein atypical protein kinase C lambda/iota (aPKC lambda) is associated with cell proliferation through unknown mechanisms. In endothelial cells, suppression of aPKC lambda impairs proliferation despite hyperactivated mitogenic signaling. Here we show that aPKC lambda phosphorylates the DNA binding domain of forkhead box O1 (FoxO1) transcription factor, a gatekeeper of endothelial growth. Although mitogenic signaling excludes FoxO1 from the nucleus, consequently increasing c-Myc abundance and proliferation, aPKC lambda controls c-Myc expression via FoxO1/miR-34c signaling without affecting its localization. We find this pathway is strongly activated in the malignant vascular sarcoma, angiosarcoma, and aPKC inhibition reduces c-Myc expression and proliferation of angiosarcoma cells. Moreover, FoxO1 phosphorylation at Ser218 and aPKC expression correlates with poor patient prognosis. Our findings may provide a new therapeutic strategy for treatment of malignant cancers, like angiosarcoma.

2019-11-12 | PXD011595 | Pride

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

Effect of conditional knockout of Prkci (atypical PKC iota/lambda coding gene) in mouse enterocytes reveals robust innate immunity transcriptomic response

Project description:Atypical PKCiota/lambda is a key effector of the PAR polarity complex which is considered a master determinant of apico-basal polarity in single-layered epithelial cells. In polarized epithelial cells aPKC is exquisitely localized by the PAR6 partner to a belt nearby the tight junctions. Surprisingly, tissue specific knock out of the transgenic floxed version with villin-CRE showed a chronic inflammation phenotype. The observations were made in three different independent transgenic mouse lines and published by three different groups including ours (PMID: 27226486; PMID: 30552022; PMID: 21744423 ), which is reassuring for reproducibility. An additional double KO in both aPKC isoforms further confirmed the results (PMID: 30552022 ). The animals were viable and there was not strong diarrheal or constipation phenotype characteristic of polarity defects in intestinal epithelia. With few exceptions such as ezrin localization, apical polarity markers were generally well polarized. There were changes in cytokine expression by epithelial cells and infiltration of CD8+ T cells (PMID: 27226486; PMID: 30552022). The goal of the study was to get an unbiased catalog of the transcriptional changes induced by aPKC iota/lambda defect in intestinal epithelial cells to understand the ontology of gene expression downstream of the PAR polarity complex. The results are consistent with broad changes in NF-kB and IFN dependent transcriptional pathways, possibly mediated by ROCK and Med17 downstream of aPKCiota/lambda (PMID: 2722648; PMID: 33596087). This study was published in PMID: 33596087.

2023-06-15 | GSE235056 | GEO

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