Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Identification of novel SCF FBXW7 substrates in asynchronous and mitotic cells

ABSTRACT: FBXW7 loss-of-function has been implicated in chemoresistance against antimicrotubule drugs. FBXW7 is frequently mutated in human cancers and the identification of FBXW7 substrates, which could be involved in this phenotype, is a major task.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Simon Haenle-Kreidler

LAB HEAD: Ingrid Hoffmann

PROVIDER: PXD035501 | Pride | 2022-12-02

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Bert_171211_P0524_PH_KR_2_percent_T_R1.hdf5	Other
	Bert_171211_P0524_PH_KR_2_percent_T_R1.mgf	Mgf
	Bert_171211_P0524_PH_KR_2_percent_T_R1.raw	Raw
	Coomassie_gel.PNG	Other
	F062764.dat	Other

Items per page:

1 - 5 of 11

Publications

The SCF-FBXW7 E3 ubiquitin ligase triggers degradation of histone 3 lysine 4 methyltransferase complex component WDR5 to prevent mitotic slippage.

Hänle-Kreidler Simon S Richter Kai T KT Hoffmann Ingrid I

The Journal of biological chemistry 20221114 12

During prolonged mitotic arrest induced by antimicrotubule drugs, cell fate decision is determined by two alternative pathways, one leading to cell death and the other inducing premature escape from mitosis by mitotic slippage. FBWX7, a member of the F-box family of proteins and substrate-targeting subunit of the SKP1-CUL1-F-Box E3 ubiquitin ligase complex, promotes mitotic cell death and prevents mitotic slippage, but molecular details underlying these roles for FBWX7 are unclear. In this study ...[more]

PMID: 36395886

Similar Datasets

Tick (Ixodes ricinus) salivary antigens by LC-MS/MS

Project description:Here, we challenged rabbits with repeated feeding of Ixodes ricinus adults and observed the formation of specific antibodies against several tick salivary proteins. To identify the salivary antigens, isolated immunoglobulins from repeatedly infested rabbits were utilised for a pull-down from the saliva of pilocarpine-treated ticks. Eluted antigens were separated on 1D SDS-PAGE and analysed by peptide mass fingerprinting. To increase the authenticity of immunogens identified, we also performed, for the first time, de novo assembly of the sialome from I. ricinus females fed for six days, a timepoint used for pilocarpine-salivation.

2021-09-09 | PXD021370 | Pride

Proteomic analysis of Kveim reagent identifies targets of cellular immunity in sarcoidosis

Project description:Kveim-reagent (Kv) skin testing was a historical method of diagnosing sarcoidosis. Intradermal injection of treated sarcoidosis spleen tissue resulted in a granuloma response at injection site by 4-6 weeks. Previous work indicates proteins as the possible trigger of this reaction. We aimed to identify Kv-specific proteins and characterise the ex vivo response of Peripheral Blood Mononuclear Cells (PBMCs) from sarcoidosis, tuberculosis and healthy control patients when stimulated with both Kv and selected Kv-specific proteins.

2017-01-31 | PXD005150 | Pride

Cell membrane proteome analysis in HEK293T cells challenged with α-Synuclein amyloids

Project description:Amyloids interact with plasma membranes. Extracellular amyloids cross the plasma membrane barrier. Internalized extracellular amyloids are reported to trigger amyloidogenesis of endogenous proteins in recipient cells. To what extent these extracellular and intracellular amyloids perturb the plasma membrane proteome is not investigated. Using α-Synuclein as a model amyloid protein, we performed membrane shaving followed by mass spectrometry experiment to identify the conformational changes in the cell surface proteins after extracellular amyloid challenge. We also performed membrane proteomics after the biogenesis of intracellular α-Synuclein amyloids. Our results suggest that promiscuous interaction with extracellular amyloids stochastically alter the conformation of plasma membrane proteins. This affects the biological process through the plasma membrane and result in loss in cell viability. Cells that survive the extracellular amyloid shock can grow normally and gradually develop intracellular amyloids which do not directly impact the plasma membrane proteome and associated biological processes. Thus, α-Synuclein amyloids can damage the plasma membrane and related processes only during cell to cell transfer and not during their intracellular biogenesis.

2024-07-09 | PXD046280 | Pride

"In-gel cross-linking mass spectrometry (IGX-MS) of proteins and protein complexes"

Project description:Cross-linking mass spectrometry has developed into an important method to study protein structures and interactions. The in-solution cross-linking workflows involve time and sample consuming steps and do not provide sensible solutions for differentiating cross-links obtained from co-occurring protein oligomers, complexes, or conformers. Here we developed a cross-linking workflow combining blue native PAGE with in-gel cross-linking mass spectrometry (IGX-MS). This workflow circumvents steps, such as buffer exchange and cross-linker concentration optimization. Additionally, IGX-MS enables the parallel analysis of co-occurring protein complexes using only small amounts of sample. Another benefit of IGX-MS observed by experiments on GroEL and purified bovine heart mitochondria, is the substantial reduction of artificial over-length cross-links when compared to in-solution cross-linking. We next used IGX-MS to investigate the complement components C5, C6, and their hetero-dimeric C5b6 complex. The obtained cross-links were used to generate a refined structural model of the complement component C6, resembling C6 in its inactivated state. This finding shows that IGX-MS can be used to provide new insights into the initial stages of the terminal complement pathway.

2020-12-14 | PXD020014 | Pride

LC-MS confirmation of alternative YPD1 isoforms from Magnaporthe oryzae

Project description:This project aims to understand better the stress response mechanisms of components of the well known High Osmolarity Glycerol two-component regulatory system in the model organism Magnaporthe oryzae. Currently, two putative isoforms of the transfer protein YPD1 (MGG_07173) are described as theoretical proteins in the UniProt database (G4MTL0 and G4MTK9). For better understanding of signal transduction and response triggering we aimed to identify alternative isoforms that might explain the variety of triggered responses throughout the YPD1 signal transfer hub.

2021-09-10 | PXD024832 | Pride

Deglutarylation of GCDH by SIRT5 controls lysine metabolism in mice

Project description:A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be non-enzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme Sirtuin 5 (SIRT5). Here, we identify glutarylation of the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH). We show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We then demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic data indicate a novel role for SIRT5 in regulation of amino acid metabolism. Together, these data suggest a model whereby a feedback loop exists within the lysine/tryptophan oxidation pathway, in which glutaryl-CoA is produced, in turn inhibiting GCDH function. This inhibition is relieved by SIRT5 deacylation activity.

2022-02-21 | PXD018156 | Pride

NPM and NPM-MLF1 interact with chromatin remodeling complexes and influence their recruitment to specific genes

Project description:Nucleophosmin (NPM1) is either frequently mutated or subjected to chromosomal translocation in acute myeloid leukemia (AML). NPM protein is primarily located in the nucleus, but the recurrent NPMc+ mutation is characterized by cytoplasmic localization and leukemogenic properties. Similarly, the NPM-MLF1 translocation product favors the partial cytoplasmic retention of NPM. Regardless of their common cellular distribution, NPM-MLF1 malignancies engender different effects on hematopoiesis compared to NPMc+ counterparts, highlighting possible aberrant nuclear function(s) of NPM in NPMc+ and NPM-MLF1 AML. We performed a proteomics analysis and found that NPM and NPM-MLF1 interact with chromatin remodeling complexes of the ISWI family, as well as with NuRD and P/BAF complexes. Accordingly, NPM and NPM-MLF1 are recruited to transcriptionally active or repressed genes along with NuRD and P/BAF elements. Although the overall gene expression program in NPM knockdown cells is similar to that resulting from NPMc+ and is consistent with loss of nuclear function of NPM, NPM-MLF1 expression differentially altered gene transcription regulated by NPM. The abnormal gene regulation imposed by NPM-MLF1 is characterized by enhanced recruitment of NuRD to gene regulatory regions. Thus, different mechanisms orchestrate the deregulation of NPM function in NPMc+ -versus NPM1-MLF1- associated leukemia.

2019-10-18 | PXD012305 | Pride

Targeting mitochondrial translation overcomes multidrug resistance in FBXW7-deficient cells

Project description:FBXW7 is one of the most frequently mutated tumor suppressors, the deficiency of which has been associated with resistance to some anticancer therapies. Through bioinformatic analyses and genome-wide CRISPR screens, we here reveal that FBXW7 deficiency leads to multi-drug resistance (MDR), to a bigger extent than well-established MDR-drivers such as ABCB1. Proteomic data from FBXW7-deficient cells and human cancer samples identify the upregulation of mitochondrial function as a hallmark of FBXW7 deficiency, which has been previously linked to an increased resistance to chemotherapy. Accordingly, genetic or chemical targeting of mitochondria is preferentially toxic for FBXW7-deficient cells. For instance, targeting mitochondrial translation with the antibiotic Tigecycline efficiently kills FBXW7-deficient cells in vitro and in vivo, by a mechanism that involves activation of the Integrated Stress Response (ISR). Searching for additional drugs that overcome MDR in FBXW7-deficient cells, we found several targeted therapies such as Erlotinib, Dasatinib or Vemurafenib which unexpectedly also activate the ISR. Together, our study reveals that one of the most frequent mutations in cancer reduces the sensitivity to the vast majority of available therapies, and identifies a general principle to overcome such resistance.

2022-06-08 | PXD029981 | Pride

Co-immunoprecipitation coupled with mass for RNR10 in rice&Identification of ubiquitination sites in rice DNR1

Project description:RNR10 is a key factor that regulates the response of rice roots to nitrogen.In an attempt to determine the target(s) of RNR10, we performed co-immunoprecipitation (Co-IP) coupled with mass spectrometry analysis to search for RNR10 interactors.DNR1 is a downstream target gene of RNR10.Previous studies have shown that rice DNR1 is subjected to ubiquitination modification. In order to identify the ubiquitination modification sites of DNR1,we performed mass spectrometry analyses.

2023-09-30 | PXD043400 | Pride

Hybrid_Poplar_H11-11_Leaves_Local_Stress_Response_DataSet2

Project description:We investigated the transcriptional response of hybrid poplar (Populus trichocarpa x deltoides) leaves to methyl jasmonate treatment over a 24 hour time course. Experiments were conducted using clonal trees under greenhouse conditions at the University of British Columbia. We used the 15.5K poplar cDNA microarray platform previously described by Ralph et al. (Molecular Ecology 2006, 15:1275-1297). Differentially expressed genes were determined using three criteria: fold-change between methyl jasmonate-treated and tween-treated control leaves > 1.5-fold, P value < 0.05 and Q value < 0.05. This study identified > 1,000 differentially expressed genes in response to methyl jasmonate treatment. A factorial hybridization design was chosen to assess gene expression between tween-treated control leaves, and leaves subjected to methyl jasmonate treatment. For each tree, all but the lowest five mature leaves were covered with a light-weight plastic bag and then sprayed with either methyl jasmonate or tween, the solvent control. Leaves were harvested 2, 6 or 24 hours after the initiation of each treatment and total RNA was individually isolated from each tree. For each treatment and time point, equal amounts of total RNA were combined from each of the five biological replicate trees prior to cDNA microarray analysis. A total of 18 hybridizations were performed to directly compare total RNA from methyl jasmonate-treated and tween-treated control leaves at each time point, as well as among methyl jasmonate-treated leaves across time points, with dye balance.

2008-12-30 | E-GEOD-14039 | 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