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YTHDC1 lactylation promotes RCC progression by regulating phase-separation to enhance the stabilities of BCL2 and E2F2 mRNAs

ABSTRACT: To obtain the global landscape of lactylation in hypoxia-treated RCC cells, we treated cells with 24 h hypoxia to induce maximum amount of hyperlactylated proteins and performed proteome and lactylome detection upon ACHN cells. Presented here is the raw data for the lactylome.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture

DISEASE(S): Kidney Cancer

SUBMITTER: yuangui tang

LAB HEAD: junfang zheng

PROVIDER: PXD053029 | Pride | 2025-07-18

REPOSITORIES: Pride

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			Action	DRS
	C_1_Slot2-20_1_5362.d.zip	Other
	C_2_Slot2-20_1_5363.d.zip	Other
	C_3_Slot2-20_1_5364.d.zip	Other
	H24_1_Slot2-21_1_5366.d.zip	Other
	H24_2_Slot2-21_1_5367.d.zip	Other

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YTHDC1 lactylation promotes RCC progression by regulating phase-separation to enhance the stabilities of BCL2 and E2F2 mRNAs

Project description:To obtain the global landscape of lactylation in hypoxia-treated RCC cells, we treated cells with 24 h hypoxia to induce maximum amount of hyperlactylated proteins and performed proteome and lactylome detection upon ACHN cells. Presented here is the raw data for the proteome.

2025-07-18 | PXD052772 | Pride

Analysis of lactylome refines key molecular reprogramming mechanisms during oil production in Nannochloropsis oceanica

Project description:Lysine lactylation as a type of posttranslational modifications (PTMs) is recently associated with chromatin remodeling and gene transcription, but lysine lactylation of histone and non-histone proteins has not yet been studied in Nannochloropsis oceanica. To examine the prevalence and function of lactylation in N. oceanica, protein lactylation modification profiles were tracked after nitrogen deprivation for three days using 4D label-free proteome method. Under nitrogen deprivation (ND) and nitrogen repletion (NR) cultivation conditions, we mapped lactylome of proliferating microalgal cells.

2024-07-03 | PXD038775 | Pride

Analysis of Lysine Lactylation in CD4+ T cells of normal and EAU mouse

Project description:Primary CD4+ T cells were isolated from normal and EAU mice spleens and used for lactylome analysis.

2023-08-29 | PXD040514 | Pride

Lactylation of nucleus pulposus cells

Project description:Nucleus pulposus (NP) resides in hypoxic microenvironment due to the avascular structure of intervertebral disc (IVD). Intracellular lactate drives lysine lactylation (Kla) as a newly epigenetic modification. However, the impact of Kla on NPCs remains unknown. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we showed a global lactylome profiling on NPCs cultured in normoxia and hypoxia environment and found that 3510 lactylation sites on 1052 proteins in NPCs on non-histone proteins. Moreover, there are 18 proteins with 129 Kla sites exclusively detected in the normoxia group, and 117 Kla sites in 27 proteins were specific in hypoxia group. Together, our dates reveals that Kla plays an important role in regulating cellular metabolism and may contribute to IDD progression.

2025-05-06 | PXD048244 | Pride

Effects of moderate intensity exercise on liver metabolism in mice based on multi-omics analysis

Project description:Background: Physical exercise is beneficial to keep physical and mental health. The molecular mechanisms underlying exercise are still worth exploring. Methods: The healthy adult mice after six weeks of moderate-intensity exercise (experimental group) and sedentary mice (control group) were used to perform transcriptomic, proteomic, lactylation modification, and metabolomics analysis. In addition, gene sets related to hypoxia, glycolysis, and fatty acid metabolism were used to aid in the screening of hub genes. The mMCP-counter was employed to evaluate infiltration of immune cells in murine liver tissues. Results: Transcriptomics analysis revealed 82 intersection genes related to hypoxia, glycolysis, and fatty acid metabolism. Proteomics and lactylation modification analysis identified 577 proteins and 141 differentially lactylation modification proteins. By overlapping 82 intersection genes with 577 differentially expressed proteins and 141 differentially lactylation modification proteins, three hub genes (Aldoa, Acsl1, and Hadhb) were obtained. The immune infiltration analysis revealed a decreased score for monocytes/macrophages and an increased score for endothelial cells in the experimental group. Then, 459 metabolites in positive mode and 181 metabolites in negative mode were identified. The “Metabolic pathways” (mmu01100) was a common pathway between intersection genes-enriched pathways and metabolites-enriched pathways. Conclusion: These findings highlight the pivotal roles of hub genes in the glycolysis and fatty acid metabolism under the context of chronic exercise.

2025-02-10 | PXD057080 | Pride

GABA regulates IL-1β production in macrophages

Project description:Neurotransmitters have been well-documented to determine immune cell fates; however, whether and how γ-amino butyric acid (GABA) shapes the function of innate immune cells is still obscure. Here, we demonstrated that GABA orchestrates macrophage maturation and inflammation. GABA treatment during macrophage maturation inhibits interleukin (IL)-1β production from inflammatory macrophages. Mechanistically, GABA enhances succinate-FAD-lysine demethylase1 (LSD1) signaling to regulate the histone demethylation of Bcl2l11 and Dusp2, lowering the formation of NLRP3-ASC-Caspase-1 complex. Meanwhile, GABA-succinate axis lowers succinylation of mitochondrial proteins to promote mitochondrial oxidative phosphorylation (OXPHOS). We also found that GABA alleviates the LPS-induced sepsis as well as high-fat diet-induced obesity in mice. Our study proves that GABA is potential in lessening the pro-inflammatory macrophage responses associating with metabolic reprogramming and protein succinylation, thus providing a strategy for treating macrophage-related inflammatory diseases.

2022-11-29 | PXD037901 | Pride

Crotonylomics sequencing of human non small cell lung cancer cell lines

Project description:Crotonylation is a crotonyl-coenzyme A (CoA)-mediated post-translational modification best known for its roles in epigenetic regulation. Histone lysine crotonylation (Kcr) has been reported to be involved in tumor-related biological functions such as DNA damage repair and immune infiltration. Here we find that abnormal reduction of histone Kcr significantly correlates with a poor response to epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in in-house-established drug-resistant models of lung cancer cell lines, and in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. The crotonyl-CoA-producing enzyme ACSS2 is the key regulator of the resistance-related change of crotonylation. Quantitative crotonylomic, transcriptomic and epigenomic analyses reveal that EGFR-TKI resistance is accompanied by reduced levels of histone 3 lysine 56 crotonylation (H3K56cr) on chromatin, which inhibits transcription of HNF1A and activates the PI3K/AKT signaling pathway. Studies of patient-derived organoids (PDOs) and resistant lung cancer CDX and PDX models treated with a novel histone decrotonylase (HDCR) inhibitor, S67, demonstrate that up-regulation of H3K56cr sensitizes cells to the effect of EGFR-TKIs. These findings uncover the role of histone Kcr in resistance to EGFR-TKIs and suggest a new combination therapy in lung cancer.

2025-09-22 | PXD053030 | Pride

Staphylococcus aureus LC-MSMS lactylation

Project description:To extensively elucidate protein lactylation (Kla), a proteome-wide analysis of lactylation was carried out in Staphylococcus aureus. Proteins extracted from Staphylococcus aureus were digested by trypsin and anti-lactyl lysine antibody was used to enrich the lactylated peptides, which were determined by following LC-MS/MS analysis.

2024-10-08 | PXD046022 | Pride

Comprehensive ubiquitomics characterization identify biomarkers of liver cancer subtypes

Project description:Hepatocellular carcinoma (HCC) has been widely studied at multi-omics level, but little is known about its specific ubiquitination, a major post-translational modification (PTM). In this study, we performed the ubiquitomics data collected from 85 HCC tumors and 18 adjacent normal tissues (ANTs) to establish the ubiquitomic profiles of HCC and reveal tumor-associated characteristics with prognosis and clinical outcomes. Ubiquitomic based stratification of HCC revealed three subtypes related to different clinical and molecular features, suggesting ubiquitomics have the potential to further understand the relationship between ubiquitination levels of proteins and different molecular and clinical features of HCC patients. XAD1—XAD18 --- HCC adjacent normal tissues XC1—XC85--- HCC tumor tissues

2025-04-07 | PXD047211 | Pride

Lysine acetylation of DosR regulates the hypoxia response of Mycobacterium tuberculosis

Project description:Tuberculosis caused by Mycobacterium tuberculosis (Mtb) infection remains a huge global public health problem. One striking characteristic of Mtb is its ability to adapt to hypoxia, and thus ensuing transition to dormant state for persistent infection, but how the hypoxia responses of Mtb is regulated remains largely unknown. Here, we performed a quantitative acetylome analysis to compare the acetylation profile of Mtb under aeration and hypoxia, and showed that 377 acetylation sites in 269 proteins of Mtb were significantly change under hypoxia. Especially, deacetylation of Dormancy Survival Regulator (DosR) at K182 promoted the hypoxia response of Mtb and enhanced transcription of DosR-targeted genes. Mechanistically, recombinant DosRK182R protein demonstrated enhanced DNA-binding activity in comparison with DosRK182Q protein. Moreover, Rv0998 was identified as an acetyltransferase that mediates the acetylation of DosR at K182. Deletion of Rv0998 also promoted the adaption of Mtb to hypoxia and transcription of DosR-targeted genes. Mice infected with Mtb strain containing acetylation-defective DosRK182R or lacking Rv0998 had much lower bacterial counts, and less severe histopathological impairments compared with those infected with the wild-type strain. Our findings suggest that hypoxia induces the deacetylation of DosR, which in turn increases its DNA binding ability to promote the transcription of target genes, allowing Mtbto transit to dormancy under hypoxia.

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