Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Differentially secreted proteins in KMT5B deficient-cells compared to their isogenic clone KMT5B wild-type assessed by mass spectrometry

ABSTRACT: In patient-derived DIPG models from multiple patients, with both H3K27M mutation and EZHIP overexpression, were generated CRISPR/Cas9-engineered and subclonal isogenic cells with KMT5B and/or KMT5C deficiency.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

SUBMITTER: James Wright

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD026670 | Pride | 2021-07-20

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	KK01_TMT5plex_2hr_3hr.msf	Msf
	KK01_TMT5plex_2hr_3hr.pdResult	Other
	KK03_TMT6plex.msf	Msf
	KK03_TMT6plex.pdResult	Other
	Lumos1_KK01_TMT5plex_P01.raw	Raw

Items per page:

1 - 5 of 25

Similar Datasets

Genetic determinants of genomic stability identified by comprehensive in vivo analyses of micronucleus formation

Project description:Genomic instability due to defective DNA damage response or arising from mitotic chromosomal imbalance can lead to sequestration of DNA in aberrant extranuclear structures called micronuclei (MN). Although MN are a hallmark of genomic instability associated diseases and ageing, the catalogue of genetic players that regulate their generation remains to be determined. Here analysed 996 mouse mutant lines, revealing 143 factors whose loss significantly increases (71) or decreases (72) MN formation. Most such genes, including the Dscc1 (DNA replication and sister chromatid cohesion 1) gene, have never been studied in mouse models. We found that Dscc1 defective mice were sub-viable and displayed phenotypes like the clinical characteristics of cohesinopathy patients. After validating the DSCC1-MN phenotype in human cells, we used genome-wide CRISPR-Cas9 screening to define its synthetic lethal and synthetic viable interactors. Perhaps surprisingly, we found that loss of Sirtuin 1 (SIRT1) can rebalance/rescue phenotypes associated with DSCC1 loss in a manner paralleling restoration of SMC3 (structural maintenance of chromosomes protein 3) protein acetylation. Our study provides a resource of novel factors involved in maintenance of genomic stability and shows how this information can be used to uncover mechanisms relevant to better understand disease biology.

2023-11-17 | PXD030499 | Pride

Proteomic analysis of Dscc1 knockout mouse cells

Project description:In this project we aimed to explore the effect of Dscc1 gene loss on the proteome. Embyros from wildtype and aged matched Dssc1 null embryos were profiled.

2023-11-17 | PXD034902 | Pride

EROS/CYBC1 CONTROLS THE PHAGOCYTE RESPIRATORY BURST VIA DIRECT INTERACTION WITH GP91PHOX AND HAS A NOVEL ROLE IN NLRP3 INFLAMMASOME ACTIVATION

Project description:EROS (Essential for Reactive Oxygen Species) protein (CYBC1) is indispensable for expression of the gp91phox-p22phox heterodimer of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of chronic granulomatous disease (CGD) but its mechanism of action remains unclear. Our work describes how EROS regulates protein abundance and describes novel roles for EROS in innate and adaptive immunity. EROS acts very early in gp91phox maturation, binding the translated 58kDa precursor directly in the endoplasmic reticulum prior to glycosylation and heme incorporation, thus preventing its degradation. Its actions are distinct from that of p22phox, which is required much later in gp91phox biosynthesis. Further, EROS’s ability to regulate p22phox abundance is entirely secondary to its effect on gp91phox. EROS also regulates the expression of other proteins, including the purine receptors P2X7 and P2X1 through direct interactions.

2023-03-11 | PXD024659 | Pride

Ubiquitin-mediated modulation of necroptotic effector MLKL

Project description:We aimed to identify lysine (K) residues that are endogenously ubiquitylated upon TNF-induced necroptosis. To this end, we used a quantitative mass spectrometry-based approach. Briefly, MDFs were treated with TSZ or left untreated and protein lysates were digested with trypsin into peptides. Ubiquitylated peptides bearing the di-glycine (K-GG) remnant were enriched by immunoprecipitation with anti-K-ε-GG antibody. A total of three biological replicates were prepared and the 6 samples were labelled with Tandem Mass Tags (TMT). Samples were mixed and analysing by Liquid Chromatography-Tandem Mass Spectroscopy (LC-MS). Quantification was performed to determine the relative abundance of site-specific ubiquitylation events in each condition.

2021-04-13 | PXD018857 | Pride

DIPG harbour alterations targetable by MEK inhibitors, with acquired resistance mechanisms overcome by combinatorial inhibition

Project description:The survival of children with DIPG remains dismal, with new treatments desperately needed. In the era of precision medicine, targeted therapies represent an exciting treatment opportunity, yet resistance can rapidly emerge, playing an important role in treatment failure. In a prospective biopsy-stratified clinical trial, we combined detailed molecular profiling (methylation BeadArray, exome, RNAseq, phospho-proteomics) linked to drug screening in newly-established patient-derived models of DIPG in vitro and in vivo. We identified a high degree of in vitro sensitivity to the MEK inhibitor trametinib in samples which harboured genetic alterations targeting the MAPK pathway, including the non-canonical BRAFG469V mutation, and those affecting PIK3R1 and NF1. However, treatment of PDX models and the patient with trametinib at relapse failed to elicit a significant response. We generated trametinib-resistant clones in the BRAF_G469V model through continuous drug exposure, and identified acquired mutations in MEK1/2 (MEK1_K57N, MEK1_I141S and MEK2_I115N) with sustained pathway up-regulation. These cells showed the hallmarks of mesenchymal transition, and expression signatures overlapping with inherently trametinib-insensitive primary patient-derived cells that predicted a confirmed sensitivity to dasatinib. Combinations of trametinib with dasatinib and the downstream ERK inhibitor ulixertinib showed highly synergistic effects in vitro. These data highlight the MAPK pathway as a therapeutic target in DIPG, and show the importance of parallel resistance modelling and rational combinatorial treatments likely to be required for meaningful clinical translation.

2021-07-20 | PXD019701 | Pride

The EN-TEx Resource for Personal Functional Genomics

Project description:An overall goal of functional genomics has been to measure the impact of variants on molecular endophenotypes (e.g. gene expression levels or the degree of TF binding) and relate this to organismal traits and disease phenotypes. However, all the experiments to date have been described relative to a generic reference genome, significantly hobbling their interpretation. Here, we describe a strategy for finding significant relationships between disease variation and genomic annotation via personal functional genomics, by performing personal genome sequencing and paired functional genomics experiments, on the same individual.

2024-05-22 | PXD022787 | Pride

Hotspot SF3B1 mutations determine response to PARP inhibitors

Project description:Hotspot mutations in the spliceosomal component gene SF3B1 underpin a number of cancers and have a neomorphic function leading to global disruption of canonical splicing and aberrant splicing of hundreds of transcripts. However, the functional consequences of this misplicing and resultant genetic vulnerabilities imposed by these events are poorly understood. Through a synthetic-lethal approach we identify that SF3B1 mutant cells are selectively sensitive to PARP inhibitors. This vulnerability is preserved across multiple cell line and patent derived tumour models, independent of SF3B1 hotspot mutation and is manifested both in vitro and in vivo. These data provide the pre-clinical and mechanistic rationale for assessing SF3B1 mutations as a biomarker of single-agent PARP inhibitor response in a new patient population and may extend the clinical utility of these agents beyond BRCA mutated cancers.

2023-04-19 | PXD019046 | Pride

Cyclin B1-Cdk1 binds MAD1 and facilitates its release from the nuclear pore complex to ensure a robust Spindle Assembly Checkpoint

Project description:How the cell rapidly and completely reorganises its architecture when it divides is a problem that has fascinated for almost 150 years. We now know that the core regulatory machinery is highly conserved in eukaryotes but how these multiple protein kinases, protein phosphatases, and ubiquitin ligases are coordinated in space and time to remodel the cell in a matter of minutes remains a major question. Cyclin B-Cdk is the primary kinase that drives mitotic remodelling and here we show that it is targeted to the nuclear pore complex (NPC) by binding an acidic face of the kinetochore checkpoint protein, MAD1, where it coordinates NPC disassembly with kinetochore assembly. This localised Cyclin B1-Cdk1 activity is needed for the proper release of MAD1 from the embrace of TPR at the nuclear pore so that it can be recruited to kinetochores before nuclear envelope breakdown to maintain genomic stability.

2020-06-29 | PXD017202 | Pride

Multifactorial remodeling of the cancer immunopeptidome by interferon gamma

Project description:In this study we combined previous transcriptomics and immunopeptidomics data with new proteomics data from untreated and IFNg-treated CRC PDOs to dissect mechanisms that lead to remodeling of the immunopeptidome through IFNg treatment (this is from the paper introduction, let me know if it needs any stylistic changes). · Experiment description: The cells were grown in DMEM/F12 media with 20% fetal bovine serum, 1X Glutamax, 100 units/ml penicillin/streptomycin and 2% matrigel, and treated with 600ng/mL IFNg for 48 hours before harvesting. Cells were washed twice with ice-cold PBS then snap-frozen.

2023-09-29 | PXD031634 | Pride

Quantitative proteomic analysis of Survival Motor Neuron (SMN) missense mutants in Drosophila

Project description:Spinal Muscular Atrophy (SMA) is a devastating neuromuscular disease caused by hypomorphic loss of function in the Survival Motor Neuron (SMN) protein. SMA presents across broad spectrum of disease severity. Unfortunately, vertebrate models of intermediate SMA have been difficult to generate and are thus unable to address key aspects of disease etiology. To address these issues, we developed a Drosophila model system that recapitulates the full range of SMA severity, allowing studies of pre-onset biology as well as late-stage disease processes. In this study, TMT-based quantitative proteomic profiling was performed on mild and intermediate Drosophila models of SMA to elucidate proteins and pathways that contribute to the disease. Using this approach, we elaborated a role for the SMN complex in the regulation of innate immune signaling.

2024-04-11 | PXD046801 | Pride

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