Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Quantitative proteomics combine with affinity MS revealed the molecular mechanism of ginsenoside anti-tumor effects

ABSTRACT: The Tandem Mass Tag (TMT) labeling quantitative proteomics technique acquired 55620 MS/MS spectra that identified 5499 proteins and 3045 modified proteins. Of these identified proteins, 224 differentially expressed proteins and modified proteins were significantly altered in non-small cell lung cancer cell lines. Bioinformatics tools for comprehensive analysis revealed that the Ras protein played a general regulatory role in many functional pathways and was probably the direct target protein of a compound in ginsenosides.

ORGANISM(S): Homo Sapiens

SUBMITTER: Wang Zhihua

PROVIDER: PXD020149 | iProX | Sun Feb 17 00:00:00 GMT 2019

REPOSITORIES: iProX

ACCESS DATA

Json Xml

Publications

Quantitative Proteomics Combined with Affinity MS Revealed the Molecular Mechanism of Ginsenoside Antitumor Effects.

Wang Zhihua Z Kim Unchol U Jiao Yanting Y Li Chaowen C Guo Yingying Y Ma Xiaoyao X Jiang Min M Jiang Zhihong Z Hou Yuanyuan Y Bai Gang G

Journal of proteome research 20190329 5

Ginsenosides have previously been demonstrated to effectively inhibit cancer cell growth and survival in both animal models and cell lines. However, the specific ginsenoside component that is the active ingredient for cancer treatment through interaction with a target protein remains unknown. By an integrated quantitative proteomics approach via affinity mass spectrum (MS) technology, we deciphered the core structure of the ginsenoside active ingredient derived from crude extracts of ginsenoside ...[more]

PMID: 30860844

Similar Datasets

ABHD17 regulation of plasma membrane palmitoylation and N-Ras-dependent cancer growth

Project description:A subset of Ras proteins, including N-Ras, depend on a palmitoylation/depalmitoylation cycle to regulate their subcellular trafficking and oncogenicity. General lipase inhibitors such as Palmostatin M block N-Ras depalmitoylation, but lack specificity and target several enzymes displaying depalmitoylase activity. Here, we describe ABD957, a potent and selective covalent inhibitor of the ABHD17 family of depalmitoylases, and show that this compound impairs N-Ras depalmitoylation in human acute myeloid leukemia (AML) cells. ABD957 produced partial effects on N-Ras palmitoylation compared to Palmostatin M, but was much more selective across the proteome, reflecting a plasma membrane-delineated action on dynamically palmitoylated proteins. Finally, ABD957 impaired N-Ras signaling and the growth of NRAS-mutant AML cells in a manner that synergizes with MEK inhibition. Our findings uncover a surprisingly restricted role for ABHD17 enzymes as regulators of the N-Ras palmitoylation cycle and suggest that ABHD17 inhibitors may have value as targeted therapies for NRAS-mutant cancers.

2021-04-28 | PXD023932 | Pride

Single-cell signaling analysis reveals that Major Vault Protein facilitates RasG12C inhibitor resistance

Project description:Recently developed covalent inhibitors for RasG12C provide the first pharmacological tools to target mutant Ras-driven cancers. However, the rapid development of resistance to current clinical Ras G12C inhibitors is common. Presumably, a subpopulation of RasG12C-expressing cells adapt their signaling to evade these inhibitors and the mechanisms for this phenomenon are unclear due to the lack of tools that can measure signaling with single-cell resolution. Here, we utilized recently developed Ras sensors to profile the environment of active Ras and to measure the activity of endogenous Ras in order to pair structure (Ras signalosome) to function (Ras activity), respectively, at a single-cell level. With this approach, we identified a subpopulation of KRasG12C cells treated with RasG12C-GDP inhibitors underwent oncogenic signaling and metabolic changes driven by WT Ras at the golgi and mutant Ras at the mitochondria, respectively. Our Ras sensors identified Major Vault Protein (MVP) as a mediator of Ras activation at both compartments by scaffolding Ras signaling pathway components and metabolite channels. We found that recently developed RasG12C-GTP inhibitors also led to MVP-mediated WT Ras signaling at the golgi, demonstrating that this a general mechanism RasG12C inhibitor resistance. Overall, single-cell analysis of structure-function relationships enabled the discovery of a RasG12C inhibitor-resistant subpopulation driven by MVP, providing insight into the complex and heterogenous rewiring occurring during drug resistance in cancer.

2024-05-16 | MSV000094779 | MassIVE

Effect of the depletion of ZC3H41 (Tb927.11.1980) on the transcriptome of procyclic Trypanosome brucei

Project description:Depletion of ZC3H41 has minor effects on the transcriptome of procyclic trypanosomes. In general, ZC3H41-regulated transcripts seem to be expressed at low abundance, and almost half of them (43%) are probably non-coding, since the corresponding encoded proteins have not been detected in proteomic surveys . A transcript encoding a trans-sialidase (Tb927.11.11410) was clearly upregulated in ZC3H41-depleted cells .

2023-03-29 | GSE212921 | GEO

Covalent inhibitor of the Rho family inhibits the migration of breast cancer cells

Project description:Small GTPase proteins usually serve as molecular switches in various biological process, such as the proliferation, survival, and migration of cells. Mutations or aberrant activations of small GTPase proteins, such as Ras, are frequently observed in various kinds of cancers. Drug discovery efforts that target the Ras family proteins are making breakthroughs, while the discovery of efficient inhibitors that target the Rho family proteins is still stagnant. Protein members from the Rho family, such as RhoA and Cdc42, are key regulators of the migration and invasion of cancer cells. Thus inhibitors of the Rho family proteins are promising to become drug candidates that target cancer metastasis, which is a principal cause of cancer recurrence and chemotherapy failure. Here we show the discovery and characterization of a novel covalent inhibitor named DC-RC-063 that targets the Rho family proteins, using a combined approach of computations and experiments. Revealed by solved crystal structures, compound DC-RC-063 inhibited the activation of RhoA, by disrupting protein-protein interactions, in an allosteric manner. As compound DC-RC-063 inhibited the migration and invasion of breast cancer MDA-MB-231 cells, our findings proved that the Rho family proteins are targetable for covalent inhibitors via an allosteric mechanism. The novel binding site revealed by this inhibitor can be exploited for further development of anti-cancer drugs that target cancer metastasis.

2017-12-07 | GSE106605 | GEO

N-arachidonoyl dopamine or vehicle control treated NRAS-G12D transformed Ba/F3 cells expression data

Project description:RAS oncogenic mutations are common in human cancers, but RAS proteins have been difficult to target. We sought to identify pharmacological agents to block the RAS oncogenic signaling by a distinct mechanism. Since the biological activity of RAS proteins rely upon lipid modifications and RAS regulates lipid metabolisms in cancer cells, we screened a bioactive lipid library using a RAS specific cell viability assay. We report the discovery of a new class of inhibitors for RAS transformation. Compounds in the class represented by endocannabinoid N-arachidonoyl dopamine (NADA) can induce cell oncosis, independent of its ability to engage cannabinoid receptors. Further analyses show that NADA is more active in inhibiting the NRAS transformation and signaling than that of KRAS4B. Mechanistically, NADA blocks the plasma membrane translocation of NRAS, but not that of KRAS4B. In addition, NADA inhibits the plasma membrane translocation and neoplastic transformation of oncogenic KRAS4A. Interestingly, NADA also redistributes the cytoplasmic NRAS to the Golgi apparatus in a palmitoylation-dependent manner. The results indicate that NADA inhibits NRAS and KRAS4A plasma membrane translocation by targeting a novel molecular process. The new findings would help to develop novel targeted therapies for a broad range of human cancers. To confirm the oncogenic RAS pathway interference of NADA, we performed microarray assay to detail the gene expression pattern change in order to figure out the RAS pathway affection and further indicate the underlying mechnism of the compound function.

2016-09-08 | GSE86541 | GEO

Human serum glycoproteome - Glyco-Decipher

Project description:Identification results of peptide-spectrum matches supporting Glyco-Decipher manuscript (Glyco-Decipher: Glycan database-independent peptide matching enables discovery of new glycans and in-depth characterization of site-specific N-glycosylation). Recently, several elegant bioinformatics tools have been developed to identify glycopeptides from tandem mass spectra for site-specific glycoproteomics studies. These glycan database-dependent tools have substantially improved glycoproteomics analysis but fail to identify glycopeptides with unexpected glycans. We present a platform called Glyco-Decipher to interpret the glycoproteomics data of N-linked glycopeptides. It adopts a glycan database-independent peptide matching scheme that allows the unbiased profiling of glycans and the discovery of new glycans linked with modifications. Reanalysis of several large-scale datasets showed that Glyco-Decipher outperformed the open search method in glycan blind searching and the popular glycan database-dependent software tools in glycopeptide identification. Our glycan database-independent search also revealed that modified glycans are responsible for a large fraction of unassigned glycopeptide spectra in shotgun glycoproteomics.

2022-03-04 | PXD031025 | Pride

Affinity peptide ligands: New tools for chasing non-canonical N-phosphoproteome

Project description:Protein N-phosphorylation enrichment is faced with great difficulties due to the intrinsic instability of the N-P bond, which has seriously hindered its biological function unraveling. Current methods for N-phosphopeptides enrichment are challenging to fulfil high selectivity for all types of N-phosphorylation with minimum contamination. To address this, we reported the first affinity peptide functionalized magnetic beads for N-phosphopeptides enrichment under neutral aqueous solution. The affinity peptide, capable of binding the N-PO3 group specifically, was identified using phage display technology based on a delicate target. We demonstrated robust enrichment capacity of the peptide-modified magnetic beads across diverse biological samples, from prokaryotes to eukaryotes, as well as various organelles and tissues. Accordingly, 262 and 2307 N-phosphorylation sites were identified from E.coli and HeLa cells, which demonstrated the enhanced enrichment capability and greatly expanded the scale of N-phosphoproteome databases. Furthermore, we found that N-phosphorylation was highly enriched in the nucleus and played a vital role in regulating processes like DNA repair. Given the high efficiency and quantitative reproducibility of the method, it was found that N-phosphorylation level for kinases and proteins involved in regulation of metabolism and microtubules varied during the progression of Alzheimer's disease. Our work expands the tools library for N-phosphorylated proteome, and provides critical insights into the roles of N-phosphorylated proteins in physiology and pathology processes.

2024-12-12 | PXD058797 |

Pleiotropic roles of Msi1-like protein, Msl1, in growth, differentiation, stress response, and virulence of Cryptococcus neoformans

Project description:WD40 motif-containing Msi1-like (MSIL) proteins play pleiotropic cellular functions as a negative regulator of the Ras/cAMP-pathways and a component of chromatin assembly factor-I (CAF-I), and yet have not been studied in fungal pathogens. Here we identified and characterized an MSIL protein, Msl1, in Cryptococcus neoformans, which can cause fatal meningoencephalitis in humans. Notably, Msl1 was not a functional ortholog for the yeast Msi1 but played pleiotropic roles in C. neoformans in both cAMP-dependent and -independent manners but mainly Ras-independently. Msl1 negatively controlled antioxidant melanin production and sexual differentiation, which can be repressed by inhibiting the cAMP-signaling pathways. In contrast, Msl1 controlled thermotolerance, diverse stress responses, and antifungal drugs resistance in Ras/cAMP-independent manners. Cac2, which is the second CAF-I component, appeared to play both redundant and distinct function with Msl1. Msl1 is required for full virulence of C. neoformans. Transcriptome and proteomic analysis identified a group of Msl1-regulated genes or -interacting proteins, respectively, which mostly include stress-related genes, including HSP12, HSP78, SSA1, SSA4, and STM1. Furthermore, we identified the third putative component of CAF-1, Rlf2, in C. neoformans. In conclusion, this study demonstrated the pleiotropic roles of Msl1 in human fungal pathogen C. neoformans, providing a novel antifungal therapeutic target.

2012-08-23 | GSE40303 | GEO

Human serum glycoproteome - Glyco-Decipher

2023-09-25 | PXD045630 |

Re-analysis of glycoproteomics data with Glyco-Decipher

Project description:Reanalysis of submissions PXD005411, PXD005413, PXD005412, PXD005553, PXD005555, PXD005565 and PXD019937 using Glyco-Decipher. Identification results of peptide-spectrum matches supporting Glyco-Decipher manuscript (Glyco-Decipher: glycan database-independent peptide matching enables discovery of new glycans and in-depth characterization of site-specific N-glycosylation). Recently, several elegant bioinformatics tools have been developed to identify glycopeptides from tandem mass spectra for site-specific glycoproteomics studies. These glycan database-dependent tools have substantially improved glycoproteomics analysis but fail to identify glycopeptides with unexpected glycans. We present a platform called Glyco-Decipher to interpret the glycoproteomics data of N-linked glycopeptides. It adopts a glycan database-independent peptide matching scheme that allows the unbiased profiling of glycans and the discovery of new glycans linked with modifications. Reanalysis of several large-scale datasets showed that Glyco-Decipher outperformed the open search method in glycan blind searching and the popular glycan database-dependent software tools in glycopeptide identification. Our glycan database-independent search also revealed that modified glycans are responsible for a large fraction of unassigned glycopeptide spectra in shotgun glycoproteomics.

2022-03-04 | PXD031032 | 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