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The analysis of GSDME-NT binding proteins in the presence or absence of methionine

ABSTRACT: Our study identify that methionine inhibits N-terminus of GSDME (GSDME-NT) -mediated pyroptosis by dampening its endocytotic degradation. Thus，the binding proteins of GSDME-NT are detected in the presence or absence of Methionine for futher exploration。

ORGANISM(S): Homo Sapiens

SUBMITTER: Jun Ma

PROVIDER: PXD059954 | iProX | Sun Jan 19 00:00:00 GMT 2025

REPOSITORIES: iProX

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Methionine metabolite spermidine inhibits tumor pyroptosis by enhancing MYO6-mediated endocytosis.

Wu Jiawei J Ding Cong C Zhang Chuqing C Xu Zhimin Z Deng Zhenji Z Wei Hanmiao H He Tingxiang T Long Liufen L Tang Linglong L Ma Jun J Liang Xiaoyu X

Nature communications 20250304 1

The connection between amino acid metabolism and pyroptosis remains elusive. Herein, we screen the effect of individual amino acid on pyroptosis and identify that methionine inhibits GSDME-mediated pyroptosis. Mechanistic analyses unveil that MYO6, a unique actin-based motor protein, bridges the GSDME N-terminus (GSDME-NT) and the endocytic adaptor AP2, mediating endolysosomal degradation of GSDME-NT. This degradation is increased by the methionine-derived metabolite spermidine noncanonically by ...[more]

PMID: 40038267

Similar Datasets

The analysis of spermidine-binding proteins

Project description:Our study identify that methionine inhibits N-terminus of GSDME (GSDME-NT) -mediated pyroptosis by dampening its endocytotic degradation. This process is regulated by methionine metabolite spermidine，which can bind with proteins to regulate their biological function. Thus，the binding proteins of spermidine are detected in the presence or absence of Methionine for futher exploration。

2025-01-21 | PXD060003 |

Nigericin induced paraptosis-like cell death instead of pyroptosis in corneal keratocytes

Project description:Corneal wound healing involves complex cellular processes, including keratocyte cell death, which plays a pivotal role in initiating tissue repair. Recent studies suggest that pyroptosis, characterized by the release of pro-inflammatory factors, occurs during tissue repair which may also contribute to the inflammatory phase of corneal wound healing. In this study, we investigated the nature of cell death in human keratocytes treated with nigericin, a known pyroptosis inducer. Surprisingly, nigericin triggered a unique form of non-inflammatory cell death marked by extensive vacuolation, resembling paraptosis. Proteomic analysis revealed that our human keratocytes lack key components of the canonical pyroptosis pathway, including NLRP3, ASC, and caspase-1, potentially explaining the absence of pyroptosis in these cells. This process was further confirmed by the absence of caspase-3 activation and lack of ER stress, alongside increased autophagic marker LC3-II accumulation. These findings suggest that nigericin triggers a paraptosis-like cell death in keratocytes, rather than pyroptosis, highlighting an alternative mechanism of cell death in corneal wound healing that warrants further exploration.

2025-06-30 | PXD058468 | Pride

Elevated methionine flux drives pyroptosis evasion in persister cancer cells

Project description:Induction of cell death represents a primary goal of most anti-cancer treatments. Despite the efficacy of such approaches, a small population of “persisters” develop evasion strategies to therapy-induced cell death. While previous studies have identified mechanisms of resistance to apoptosis, the mechanisms by which persisters dampen other forms of cell death, such as pyroptosis, remain to be elucidated. Pyroptosis is a form of inflammatory cell death that involves formation of membrane pores, ion gradient imbalance, water inflow and membrane rupture. Herein, we investigate mechanisms by which cancer persisters resist pyroptosis, survive, then proliferate in the presence of tyrosine kinase inhibitors (TKI). Lung, prostate and esophageal cancer persister cells remaining after treatments exhibited several hallmarks indicative of pyroptosis resistance. The inflammatory attributes of persisters included chronic activation of inflammasome, STING, and type I interferons. Comprehensive metabolomic characterization uncovered that TKI-induced pyroptotic persisters display high methionine consumption and excessive taurine production. Elevated methionine flux or exogenous taurine maintained plasma membrane integrity via osmolyte-mediated effects. Increased dependency on methionine flux decreased the level of one carbon metabolism intermediate S-(5'-adenosyl)-L-homocysteine, a determinant of cell methylation capacity. The consequent increase in methylation potential induced DNA hypermethylation of genes regulating metal ion balance and intrinsic immune response. This enabled thwarting TKI resistance by using the hypomethylating agent decitabine. In summary, the evolution of resistance to pyroptosis can occur via a stepwise process of physical acclimation and epigenetic changes without existing or recurrent mutations.

2022-12-02 | GSE219044 | GEO

Characterization of methionine dependence in melanoma cells [HumanMethylationEPIC]

Project description:Dietary methionine restriction is associated with a reduction in tumor growth in preclinical studies and an increase in lifespan in animal models. The mechanism by which methionine restriction inhibits tumor growth while sparing normal cells is incompletely understood, except for the observation that normal cells can utilize methionine or homocysteine interchangeably (methionine independence) while most cancer cells are strictly dependent on methionine availability. Here, we compared a typical methionine dependent and a rare methionine independent melanoma cell line. We show that replacing methionine, a methyl donor, with homocysteine generally induced hypomethylation in gene promoters. This decrease was similar in methionine dependent versus methionine independent cells. There was only a low level of pathway enrichment, suggesting that the hypomethylation is generic rather than gene specific. Whole proteome and transcriptome were also analyzed. This analysis revealed that contrarily to the effect on methylation, the replacement of methionine with homocysteine had a much greater effect on the transcriptome and proteome of methionine dependent cells than methionine independent cells. Interestingly, the methionine adenosyltransferase 2A (MAT2A), responsible for the synthesis of s-adenosylmethionine from methionine, was equally strongly upregulated in both cell lines. This suggests that the absence of methionine is equally detected but trigger different outcomesin methionine dependent versus independent cells. Our analysis reveals the importance of cell cycle control, DNA damage repair, translation, nutrient sensing, oxidative stress and tight junctions in the cellular response to methionine stress in melanoma.

2023-05-03 | GSE225944 | GEO

Characterization of methionine dependence in melanoma cells [RNA-seq]

2023-05-03 | GSE225945 | GEO

CD4+ T cells in presence or absence of Ikaros

Project description:CD4+ T cells in presence or absence of Ikaros

| PRJNA662885 | ENA

Systematic discovery of endogenous human ribonucleoprotein complexes

Project description:An exploration of human protein complexes in the presence and absence of RNA reveals endogenous ribonucleoprotein complexes

2019-09-19 | GSE137651 | GEO

Differential expression of Staphylococcus equorum grown alone and in the presence of fungi

Project description:A specific interaction between the mold Scopulariopsis and S. equorum shifts the composition of the Staphylococcus community from dominance by a strong competitor, S. xylosus, to dominance by a weak competitor, S. equorum. To better understand specific genes and pathways involved with Scopulariopsis stimulation of S. equorum, we used RNA-seq to identify CDS that were up- and down-regulated in the genome of S. equorum in the presence and absence of the mold Scopulariopsis. We compared the effect of Scopulariopsis on the S. equorum transcriptome to the effect of Penicillium on the S. equorum transcriptome to determine why Scopulariopsis had such strong growth promotion effects relative to Penicillium. In the presence of both molds, Methionine biosynthesis and uptake pathways are strongly down-regulated, while Thiamine biosynthesis is up-regulated, suggesting that bacterial-fungal interactions alter the availability of free amino acids and nutrients in cheese environment for both partners. In the presence of Scopulariopsis only, there is a decrease in expression of genes involved with iron acquisition and the production of siderophores, notably the staphyloferrin B operon.

2016-09-27 | GSE75505 | GEO

Transcriptome of Helicobacter pylori in presence or absence of the cagPAI

Project description:Transcriptome of Helicobacter pylori in presence or absence of the cagPAI

| PRJNA945073 | ENA

T cells activated in the presence or absence of TLR agonists

Project description:T cells activated in the presence or absence of TLR agonists

| PRJNA432950 | ENA