Exocyst protein subnetworks integrate Hippo and mTOR signaling to promote virus detection and cancer
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE176496 | GEO | 2021/06/10
REPOSITORIES: GEO
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Project description:The exocyst is an evolutionarily conserved protein complex that regulates vesicular trafficking and scaffolds signal transduction. Key upstream components of the exocyst include monomeric RAL GTPases, which help mount cell-autonomous responses to trophic and immunogenic signals. Here, we present a quantitative proteomics-based characterization of dynamic and signal-dependent exocyst protein interactomes. Under viral infection, an Exo84 exocyst subcomplex assembles the immune kinase Protein Kinase R (PKR) together with the Hippo kinase Macrophage Stimulating 1 (MST1). PKR phosphorylates MST1 to activate Hippo signaling and inactivate Yes Associated Protein 1 (YAP1). By contrast, a Sec5 exocyst subcomplex recruits another immune kinase, TANK binding kinase 1 (TBK1), which interacted with and activated mammalian target of rapamycin (mTOR). RALB was necessary and sufficient for induction of Hippo and mTOR signaling through parallel exocyst subcomplex engagement, supporting the cellular response to virus infection and oncogenic signaling. This study highlights RALB-exocyst signaling subcomplexes as mechanisms for the integrated engagement of Hippo and mTOR signaling in cells challenged by viral pathogens or oncogenic signaling.
| S-EPMC8383154 | biostudies-literature
Project description:Exocyst protein subnetworks integrate Hippo and mTOR signaling to promote virus detection and cancer
| PRJNA736436 | ENA
Project description:We describe transcriptomic changes in HMT-3522-S1 cells cultured in the acinar morphogenesis assay in reponse to either empty-nanolipoprotein stimulus, Her2-nanolipoprotien stimulus or control unstimulated cells.
2021-11-17 | GSE184648 | GEO
Project description:Detection of immunogenic proteins remains an important task for life sciences as it nourishes the understanding of pathogenicity, illuminates new potential vaccine candidates and broadens the spectrum of biomarkers applicable in diagnostic tools. Traditionally, immunoscreenings of expression libraries via polyclonal sera on nitrocellulose membranes or screenings of whole proteome lysates in 2-D gel electrophoresis are performed. However, these methods feature some rather inconvenient disadvantages. Screening of expression libraries to expose novel antigens from bacteria often lead to an abundance of false positive signals owing to the high cross reactivity of polyclonal antibodies towards the proteins of the expression host. A method is presented that overcomes many disadvantages of the old procedures. We incorporated a fusion tag prior to our genes of interest and attached the expressed fusion proteins covalently on microarrays. This enhances the specific binding of the proteins compared to nitrocellulose. Thus, it helps to reduce the number of false positives significantly. It enables us to screen for immunogenic proteins in a shorter time, with more samples and statistical reliability. We validated our method by employing several known genes from Campylobacter jejuni NCTC 11168. Four of proteins that have previously been described as immunogenic have successfully been assessed immunogenic abilities with our method. One protein with no known immunogenic behaviour before suggested potential immunogenicity. The method presented offers a new approach for screening of bacterial expression libraries to illuminate novel proteins with immunogenic features. It could provide a powerful and attractive alternative to existing methods and help to detect and identify bacterial virulence factors, vaccine candidates and potential biomarkers. The overall study was done with five technical replicates. Ten proteins derived from Campylobacter jejuni were tested regarding their immunogenic potential. The ten proteins derived from Campylobacter jejuni were fusion proteins, i.e., N-terminal HaloTag fused to: Gene <--> Protein cjaA <--> putative amino-acid transporter periplasmic solute-binding protein hisJ <--> histidine-binding protein precursor pal <--> peptidoglycan associated lipoprotein flaC <--> flagellin flaA <--> flagellin peb1a <--> bifunctional adhesin/ABC transporter aspartate/glutamate-binding protein pyrC <--> dihydroorotase (EC:3.5.2.3) pseB <--> UDP-GlcNAc-specific C4,6 dehydratase/C5 epimerase gapA <--> glyceraldehyde 3-phosphate dehydrogenase (EC:1.2.1.12) argC <--> N-acetyl-gamma-glutamyl-phosphate reductase (EC:1.2.1.38)
2011-10-26 | E-GEOD-33295 | biostudies-arrayexpress
Project description:Ultimately, the genotype of a cell and its interaction with the environment determine the cell’s biochemical state. While the cell’s response to a single stimulus has been studied extensively, a conceptual framework to model the effect of multiple environmental stimuli applied concurrently is not as well developed. In this study, we developed the concepts of environmental interactions and epistasis to explain the responses of the S. cerevisiae proteome to simultaneous environmental stimuli. We hypothesize that, as an abstraction, environmental stimuli can be treated as analogous to genetic elements. This would allow modeling of the effects of multiple stimuli using the concepts and tools developed for studying gene interactions. Mirroring gene interactions, our results show that environmental interactions play a critical role in determining the state of the proteome. We show that individual and complex environmental stimuli behave similarly to genetic elements in regulating the cellular responses to stimuli, including the phenomena of dominance and suppression. Interestingly, we observed that the effect of a stimulus on a protein is dominant over other stimuli if the response to the stimulus involves the protein. Using publicly available transcriptomic data, we find that environmental interactions and epistasis regulate transcriptomic responses as well.
2015-07-20 | PXD002371 | Pride
Project description:Detection of immunogenic proteins remains an important task for life sciences as it nourishes the understanding of pathogenicity, illuminates new potential vaccine candidates and broadens the spectrum of biomarkers applicable in diagnostic tools. Traditionally, immunoscreenings of expression libraries via polyclonal sera on nitrocellulose membranes or screenings of whole proteome lysates in 2-D gel electrophoresis are performed. However, these methods feature some rather inconvenient disadvantages. Screening of expression libraries to expose novel antigens from bacteria often lead to an abundance of false positive signals owing to the high cross reactivity of polyclonal antibodies towards the proteins of the expression host. A method is presented that overcomes many disadvantages of the old procedures. We incorporated a fusion tag prior to our genes of interest and attached the expressed fusion proteins covalently on microarrays. This enhances the specific binding of the proteins compared to nitrocellulose. Thus, it helps to reduce the number of false positives significantly. It enables us to screen for immunogenic proteins in a shorter time, with more samples and statistical reliability. We validated our method by employing several known genes from Campylobacter jejuni NCTC 11168. Four of proteins that have previously been described as immunogenic have successfully been assessed immunogenic abilities with our method. One protein with no known immunogenic behaviour before suggested potential immunogenicity. The method presented offers a new approach for screening of bacterial expression libraries to illuminate novel proteins with immunogenic features. It could provide a powerful and attractive alternative to existing methods and help to detect and identify bacterial virulence factors, vaccine candidates and potential biomarkers.
2011-10-27 | GSE33295 | GEO
Project description:MotivationBacksplicing of RNA results in circularized rather than linear transcripts, known as circular RNA (circRNA). A recently discovered and poorly understood subset of circRNAs that are composed of multiple genes, termed fusion-derived circular RNAs (fcircRNAs), represent a class of potential biomarkers shown to have oncogenic potential. Detection of fcircRNAs eludes existing analytical tools, making it difficult to more comprehensively assess their prevalence and function. Improved detection methods may lead to additional biological and clinical insights related to fcircRNAs.ResultsWe developed the first unbiased tool for detecting fcircRNAs (INTEGRATE-Circ) and visualizing fcircRNAs (INTEGRATE-Vis) from RNA-Seq data. We found that INTEGRATE-Circ was more sensitive, precise and accurate than other tools based on our analysis of simulated RNA-Seq data and our tool was able to outperform other tools in an analysis of public lymphoblast cell line data. Finally, we were able to validate in vitro three novel fcircRNAs detected by INTEGRATE-Circ in a well-characterized breast cancer cell line.Availability and implementationOpen source code for INTEGRATE-Circ and INTEGRATE-Vis is available at https://www.github.com/ChrisMaherLab/INTEGRATE-CIRC and https://www.github.com/ChrisMaherLab/INTEGRATE-Vis.
| S-EPMC10516643 | biostudies-literature
Project description:8 ligand), and compared these samples to unstimulated counterparts. Both methods, RNA-seq and microarray, gave very similar results and showed that Hiltonol and pRNA lead to almost identical changes in the transcriptome of cDC1 mDCs. A gene ontology (GO) term analysis suggested that these changes were mainly related to activation and maturation pathways, including induction of type I IFN and IL-12 transcription, while pathways related to adverse effects or cell damage were not strongly affected. The combination of both reagents in the DC cultures gave a very similar result as compared to either stimulus alone, suggesting no synergistic effect. Together, our results indicate that both stimuli are potent clinical grade adjuvants with comparable effects to mature cDC1 mDCs within an immunogenic profile in short-term cultures suitable to be used in immunotherapy.
2020-04-01 | GSE142630 | GEO
Project description:The objective of this study was to identify novel genes whose expression is sensitive to anabolic stimuli. We used microarrays to detail the change in gene expression within the tibialis anterior muscle following an anabolic stimulus. In this case, the anabolic stimulus was nutrient consumption.
2019-05-23 | GSE125233 | GEO
Project description:Stimulation of dendritic cells (DC) is considered critical in cancer immunotherapy. BATF-3–dependent subsets, that express in humans BDCA-3 (CD141), promote CD8 T-cell cross-priming against tumor antigens. Here, we evaluate two clinical grade stimuli for peripheral blood cDC1 myeloid dendritic cells (mDCs), a rare DC subset that is currently being explored for use in immunotherapy. In contrast to routine evaluation methods, which focus on predefined maturation markers on the surface or factors released from the activated cells, we applied an unbiased transcriptome-based method using both RNA-sequencing (RNA-seq) and microarrays. Specifically, we analyzed the mRNA of cDC1 mDCs from five human donors upon activation with two clinical-grade adjuvants, Hiltonol (poly IC, a TLR3 ligand, called Stimulus 1 in the description below) and protamine RNA (pRNA, aTLR7/8 ligand, Stimulus 2), and compared these samples to unstimulated counterparts. Both methods, RNA-seq and microarray, gave very similar results and showed that Hiltonol and pRNA lead to almost identical changes in the transcriptome of cDC1 mDCs. A gene ontology (GO) term analysis suggested that these changes were mainly related to activation and maturation pathways, including induction of type I IFN and IL-12 transcription, while pathways related to adverse effects or cell damage were not strongly affected. The combination of both reagents in the DC cultures gave a very similar result as compared to either stimulus alone, suggesting no synergistic effect. Together, our results indicate that both stimuli are potent clinical grade adjuvants with comparable effects to mature cDC1 mDCs within an immunogenic profile in short-term cultures suitable to be used in immunotherapy.
2023-09-30 | GSE239895 | GEO