Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A systems chemoproteomic analysis of acyl-CoA signaling networks

ABSTRACT: Acyl-CoAs are essential for life. These metabolites serve as fundamental cellular building blocks in the biosynthesis of lipids, intermediates in energy production via the TCA cycle, and essential precursors for reversible protein acetylation. Each of these roles are dependent on acyl-CoA/protein interactions, physical contacts that can regulate protein function via a variety of mechanisms. We utilized systems-level analyses to characterize novel protein networks that interact with metabolic acyl-CoAs, and evaluate the potential of these interactions to facilitate enzyme activity or non-enzymatic acylation. Our studies provide a roadmap for integrating chemoproteomic data with systems biology analysis, and establish a novel resource for understanding the diverse signaling roles of acyl-CoAs in biology and disease.

INSTRUMENT(S): LTQ

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Michaella Levy

LAB HEAD: Laurence Florens

PROVIDER: PXD013157 | Pride | 2019-11-21

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	DTASelect.params	Other
	Hs_HeLa-AP_Lys-CoA_0nM-CoA_Ti_L5_4.mzid.gz	Mzid
	Hs_HeLa-AP_Lys-CoA_0nM-CoA_Ti_L5_401.RAW	Raw
	Hs_HeLa-AP_Lys-CoA_0nM-CoA_Ti_L5_401.mgf	Mgf
	Hs_HeLa-AP_Lys-CoA_0nM-CoA_Ti_L5_401.ms2	Other

Items per page:

1 - 5 of 1701

Similar Datasets

Thermococcus kodakarensis proteins expressed at various temperatures reveals changes in RNA modifications

Project description:Thermococcus kodakarensis is a thermophilic archaea used in this study to determine how changes in growth temperature affect protein expression. This organism was chosen, in part, due to the simplified proteome and potential protein stability gained when analyzing proteins at room temperature. Two temperatures were used as well as one knockout cell line to determine the differences in protein expression. Specifically, changes in protein expression levels were used in conjunction with other data to determine the changing levels of RNA modification based on expression temperature.

2020-02-17 | PXD014814 | Pride

Arabidopsis thaliana

Project description:Response of Arabidopsis thaliana seedlings to acyl-CoAs

| PRJNA380922 | ENA

Fatty acid transport protein 2 interacts with ceramide synthase 2 to regulate ceramide synthesis

Project description:Dihydroceramide is generated via the action of (dihydro)ceramide synthases (CerSs), which use two substrates, namely sphinganine and fatty acyl CoAs. Sphinganine is generated via the sequential activity of two integral membrane proteins located in the endoplasmic reticulum. Less is known about the source of supply of the fatty acyl CoAs, although a number of cytosolic proteins in the pathways of acyl CoA generation have been shown to modulate ceramide synthesis via direct or indirect interaction with the CerSs. We now demonstrate, by proteomic analysis of immunoprecipitated proteins, that fatty acid transporter protein 2 (FATP2) (also known as very long-chain acyl-CoA synthetase) directly interacts with CerS2 in mouse liver. Studies in cultured cells demonstrated that other members of the FATP family can also interact with CerS2, with the interaction dependent on both proteins being catalytically active. Transfection of cells with FATP1, FATP2 or FATP4 increased ceramide levels although only FATP2 and 4 increased dihydroceramide levels, consistent with their known intracellular locations. Finally, lipofermata, an FATP2 inhibitor which is believed to directly impact tumor cell growth via modulation of FATP2, decreased de novo dihydroceramide synthesis, suggesting that some of the proposed therapeutic effects of lipofermata may actually be mediated via (dihydro)ceramide rather than directly via acyl CoA generation

2022-04-04 | PXD031088 | Pride

Probing the Sensitivity of the Lumos Mass Spectrometer using a Standard Reference Protein in a Complex Background

Project description:we determined the sensitivity of the Lumos mass spectrometer using the NIST monoclonal antibody reference material at various concentrations to detect its peptides in a background of S. cerevisiae whole cell lysate, which was kept at a constant concentration.

2018-09-12 | PXD009441 | Pride

Effect of Nudt7 overexpression on the global transcriptome of mouse liver in the fasted state

Project description:RNAseq analysis was conducted to complement the targeted and untargeted metabolomics analysis of livers overexpressing the CoA-degrading enzyme Nudt7 or GFP (control). Lipid metabolism requires coenzyme A (CoA), which is found in multiple subcellular compartments including the peroxisomes. In the liver, CoA levels are dynamically adjusted between the fed and fasted states. The elevation in CoA levels that occurs during fasting is driven by increased synthesis but also correlates with decreased expression of Nudt7, the major CoA-degrading enzyme in the liver. Nudt7 resides in the peroxisomes and we overexpressed this enzyme in mouse livers to determine its effect on the size and composition of the hepatic CoA pool in the fed and fasted states. Nudt7 overexpression did not change total CoA levels but decreased the concentration of short-chain acyl-CoAs and choloyl-CoA in fasted livers, when endogenous Nudt7 activity was lowest. The effect on these acyl-CoAs correlated with a significant decrease in the hepatic bile acid content and in the rate of peroxisomal fatty acid oxidation, as estimated by targeted and untargeted metabolomics, combined with the measurement of fatty acid oxidation in intact hepatocytes. Identification of the CoA species and metabolic pathways affected the overexpression on Nudt7 in vivo supports the conclusion that the nutritionally-driven modulation of Nudt7 activity could contribute to the regulation of the peroxisomal CoA pool and peroxisomal lipid metabolism.

2019-03-08 | GSE125237 | GEO

NUDT7 Regulates Total Hepatic CoA Levels and the Composition of the Intestinal Bile Acid Pool in Male Mice Fed a Western Diet

Project description:Nudix hydrolase 7 (NUDT7) is a peroxisomal (acyl-)CoA-degrading enzyme that is highly expressed in the liver. We previously showed that liver-specific NUDT7 overexpression affects peroxisomal lipid metabolism, but does not prevent the increase in total liver CoA levels that occurs with fasting. Herein, we show that deletion of Nudt7 alters the composition of the hepatic acyl-CoA pool in mice fed a low fat diet, but only in males fed a western diet does the lack of NUDT7 increase total liver CoA levels. This effect is driven by the accumulation of medium-chain dicarboxylic acyl-CoAs, which are products of the oxidation of dicarboxylic fatty acids in the peroxisomes. We also show that, under conditions of increased cholesterol intake and elevated bile acid synthesis, Nudt7 deletion increases the production of tauro-muricholic acids, decreasing the hydrophobicity index of the intestinal bile acid pool and increasing fecal cholesterol excretion. Collectively, our findings reveal a key role for NUDT7 in the regulation of the final products of bile acid synthesis and dicarboxylic fatty acid oxidation

2022-11-25 | GSE207914 | GEO

Response of Arabidopsis thaliana seedlings to acyl-CoAs

Project description:Floodings already have a nearly 60% share in the worldwide damage to crops provoked by natural disasters. Climate change will cause plants to be even more frequently exposed to oxygen limiting conditions (hypoxia) in the near future due to heavy precipitation and concomitant waterlogging or flooding events in large areas of the world. Although the homeostatic regulation of adaptive responses to low oxygen stress in plants is well described, it remained unknown by which initial trigger the molecular response to low-oxygen stress is activated. Here, we show that a hypoxia-induced decline of the ATP level of the cell reduces LONG-CHAIN ACYL-COA SYNTHETASE (LACS) activity, which leads to a shift in the composition of the acyl-CoA pool. High oleoyl-CoA levels release the transcription factor RELATED TO APETALA 2.12 (RAP2.12) from its interaction partner ACYL-COA BINDING PROTEIN (ACBP) at the plasma membrane to induce low oxygen-specific gene expression. We show that different acyl-CoAs provoke unique molecular responses revealing a novel role as cellular signalling component also in plants. In terms of hypoxia signalling, dynamic acyl-CoA levels integrate the cellular energy status into the oxygen signalling cascade with ACBP and RAP2.12 being the central hub. The conserved nature of the ACBP:RAP2.12 module in crops and the novel mechanistic understanding of how low-oxygen stress responses are initiated by oleoyl-CoA in plants provide useful leads for enhancing future food security.

2018-04-30 | GSE97186 | GEO

A class of reactive acyl-CoA species reveals the nonenzymatic origins of protein acylation

Project description:The mechanisms underlying the formation of acyl protein modifications remain poorly understood. By investigating the reactivity of endogenous acyl-CoA metabolites, we found a class of acyl-CoAs that undergoes intramolecular catalysis to form reactive intermediates which non-enzymatically modify proteins. Based on this mechanism, we predicted, validated, and characterized the protein modification: 3-hydroxy-3-methylglutaryl(HMG)-lysine. In a model of altered HMG-CoA metabolism, we found evidence of two additional protein modifications: 3-methylglutaconyl(MGc)-lysine and 3-methylglutaryl(MG)-lysine. Using quantitative proteomics, we compared the ‘acylomes’ of two reactive acyl-CoA species, namely HMG-CoA and glutaryl-CoA, which are generated in different pathways. We found proteins that are uniquely modified by each reactive metabolite, as well as common proteins and pathways. We identified the tricarboxylic acid cycle as a pathway commonly regulated by acylation, and validated malate dehydrogenase as a key target. These data identify a fundamental relationship between reactive acyl-CoA species and proteins, and define a new regulatory paradigm in metabolism.

2017-04-11 | PXD005895 | Pride

Systems biology of prostate cancer

Project description:Systems biology of prostate cancer

| PRJEB34826 | ENA

Project description:Saccharomyces cerevisiae systems biology of ethanol

| PRJNA727478 | ENA