Protein posttranslational modifications in health and diseases: Functions, regulatory mechanisms, and therapeutic implications

MedComm, Год журнала: 2023, Номер 4(3)

Опубликована: Май 2, 2023

Protein posttranslational modifications (PTMs) refer to the breaking or generation of covalent bonds on backbones amino acid side chains proteins and expand diversity proteins, which provides basis for emergence organismal complexity. To date, more than 650 types protein modifications, such as most well-known phosphorylation, ubiquitination, glycosylation, methylation, SUMOylation, short-chain long-chain acylation redox irreversible have been described, inventory is still increasing. By changing conformation, localization, activity, stability, charges, interactions with other biomolecules, PTMs ultimately alter phenotypes biological processes cells. The homeostasis important human health. Abnormal may cause changes in properties loss functions, are closely related occurrence development various diseases. In this review, we systematically introduce characteristics, regulatory mechanisms, functions health addition, therapeutic prospects diseases by targeting associated enzymes also summarized. This work will deepen understanding promote discovery diagnostic prognostic markers drug targets

Язык: Английский

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Lactate‐induced protein lactylation: A bridge between epigenetics and metabolic reprogramming in cancer

Cell Proliferation, Год журнала: 2023, Номер 56(10)

Опубликована: Апрель 14, 2023

Lactate is not only an endpoint of glycolysis but gradually being discovered to play the role a universal metabolic fuel for energy via 'lactate shuttle' moving between cells and transmitting signals. The glycolytic-dependent metabolism found in tumours fast-growing has made lactate pivotal player reprogramming, which enables obtain abundant short time. Moreover, can provide favourable conditions tumorigenesis by shaping acidic tumour microenvironment, recruiting immune cells, etc. recently lactate-induced lactylation moves even further on pro-tumorigenesis mechanisms production, circulation utilization. As with other epigenetic modifications, modify histone proteins alter spatial configuration chromatin, affect DNA accessibility regulate expression corresponding genes. What's more, degree inseparable from spatialized concentration, builds bridge epigenetics reprogramming. Here, we review important summarize latest finding try explore therapeutic strategies oncotherapy that kill two birds one stone.

Язык: Английский

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Nucleolin lactylation contributes to intrahepatic cholangiocarcinoma pathogenesis via RNA splicing regulation of MADD

Journal of Hepatology, Год журнала: 2024, Номер unknown

Опубликована: Апрель 1, 2024

Intrahepatic cholangiocarcinoma (iCCA) is a fatal malignancy of the biliary system. The lack detailed understanding oncogenic signaling or global gene expression alterations has impeded clinical iCCA diagnosis and therapy. role protein lactylation, newly unraveled post-translational modification that orchestrates expression, remains largely elusive in pathogenesis iCCA.

Язык: Английский

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Orphan Nuclear Receptor NR4A3 Promotes Vascular Calcification via Histone Lactylation

Circulation Research, Год журнала: 2024, Номер 134(11), С. 1427 - 1447

Опубликована: Апрель 17, 2024

Medial arterial calcification is a chronic systemic vascular disorder distinct from atherosclerosis and commonly observed in patients with kidney disease, diabetes, aging individuals. We previously showed that NR4A3 (nuclear receptor subfamily 4 group A member 3), an orphan nuclear receptor, key regulator apo (apolipoprotein) A-IV-induced progression; however, its role poorly understood.

Язык: Английский

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Lactate metabolism in neurodegenerative diseases

Neural Regeneration Research, Год журнала: 2023, Номер 19(1), С. 69 - 74

Опубликована: Апрель 13, 2023

Lactate, a byproduct of glycolysis, was thought to be metabolic waste until the discovery Warburg effect. Lactate not only functions as substrate provide energy but can also function signaling molecule modulate cellular under pathophysiological conditions. The Astrocyte-Neuron Shuttle has clarified that lactate plays pivotal role in central nervous system. Moreover, protein lactylation highlights novel regulating transcription, functions, and disease development. This review summarizes recent advances metabolism its neurodegenerative diseases, thus providing optimal perspectives for future research.

Язык: Английский

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Lactate and Lactylation in the Brain: Current Progress and Perspectives

Cellular and Molecular Neurobiology, Год журнала: 2023, Номер 43(6), С. 2541 - 2555

Опубликована: Март 16, 2023

Язык: Английский

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Histone lactylation regulates cancer progression by reshaping the tumor microenvironment

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Окт. 27, 2023

As a major product of glycolysis and vital signaling molecule, many studies have reported the key role lactate in tumor progression cell fate determination. Lactylation is newly discovered post-translational modification induced by lactate. On one hand, lactylation introduced new era metabolism microenvironment (TME), on other it provided breakthrough point for elucidation interaction between metabolic reprogramming epigenetic modification. Studies shown that cells, stem cells tumor-infiltrating immune TME can participate development cancer through downstream transcriptional regulation, potential promising treatment target. This review summarized discovery effects lactylation, as well recent research histone regulating reshaping TME. We also focused strategies to enhance anti-tumor via targeting lactylation. Finally, we discussed limitations existing proposed perspectives future order further explore targets. It may provide way direction improve prognosis.

Язык: Английский

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Virus‐Induced Histone Lactylation Promotes Virus Infection in Crustacean

Advanced Science, Год журнала: 2024, Номер 11(30)

Опубликована: Июнь 14, 2024

Abstract As “non‐cellular organisms”, viruses need to infect living cells survive themselves. The virus infection must alter host's metabolisms. However, the influence of metabolites from altered metabolisms virus‐infected host on virus‐host interactions remains largely unclear. To address this issue, shrimp, a representative species crustaceans, is challenged with white spot syndrome (WSSV) in study. vivo results presented that WSSV enhanced shrimp glycolysis, leading accumulation lactate. lactate turn promoted site‐specific histone lactylation (H3K18la and H4K12la) p300/HDAC1/HDAC3‐dependent manner. H3K18la H4K12la are enriched promoters 75 target genes, which modification upregulated expression ribosomal protein S6 kinases 2 ( S6K2 ) hosts promote infection. Further data revealed virus‐encoded miR‐N20 targeted hypoxia inducible factor‐1α HIF‐1α inhibit suppression H4K12la. Therefore, findings contributed novel insights into effects underlying mechanism virus‐induced interactions, providing new targets for control

Язык: Английский

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The effects of long-term lactate and high-intensity interval training (HIIT) on brain neuroplasticity of aged mice

Heliyon, Год журнала: 2024, Номер 10(2), С. e24421 - e24421

Опубликована: Янв. 1, 2024

Extensive research has confirmed numerous advantages of exercise for promoting brain health. More recent studies have proposed the potential benefits lactate, by-product exercise, in various aspects function and disorders. However, there remains a gap understanding effects lactate dosage its impact on aged rodents. The present study first examined long-term three different doses intervention (2000 mg/kg, 1000 500 mg/kg) high-intensity interval training (HIIT) aging mice (20-22 months) as 1st experiment. Subsequently, 2nd experiment, we investigated mg/kg HIIT neuroplasticity (25-27 months). results experiment demonstrated that both (500 2000 positively impacted biomarker VEGF hippocampus mice. revealed significantly improved performance open-field, novel object recognition, passive avoidance tests. did not affect these behavioral Moreover, compared to control group, influenced angiogenesis signaling pathway (p/t-AKT/ENOS/VEGF), mitochondrial (SDHA), metabolic protein (p/t-CREB, p/t-HSL, LDH) Notably, only elevated BDNF (PGC-1α, SIRT1, BDNF) content (lactate pyruvate). In end, failed change expression p/t-MTOR, iNOS, nNOS, HIF-1α, SYNAPSIN, SIRT3, NAMPT, CS, FNDC5 Pan Lactic aid-Lysine summary, proved treatment positive functions mice, suggesting usage therapeutic strategy neurodegenerative diseases elderly population.

Язык: Английский

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A pan-cancer multi-omics analysis of lactylation genes associated with tumor microenvironment and cancer development

Heliyon, Год журнала: 2024, Номер 10(5), С. e27465 - e27465

Опубликована: Март 1, 2024

BackgroundLactylation is a significant post-translational modification bridging the gap between cancer epigenetics and metabolic reprogramming. However, association lactylation prognosis, tumor microenvironment (TME), response to drug therapy in various cancers remains unclear.MethodsFirst, expression, prognostic value, genetic epigenetic alterations of genes were systematically explored pan-cancer manner. Lactylation scores derived for each using single-sample gene set enrichment analysis (ssGSEA) algorithm. The correlation with clinical features, TME was assessed by integrating multiple computational methods. In addition, GSE135222 data used assess efficacy predicting immunotherapy outcomes. expression breast gliomas verified RNA-sequencing.ResultsLactylation significantly upregulated most types. CREBBP EP300 exhibited high mutation rates analysis. impact score varied type, protective factor KIRC, ACC, READ, LGG, UVM, risk CHOL, DLBC, LAML, OV. associated cold TME. infiltration levels CD8+ T, γδT, natural killer T cell (NKT), NK cells lower tumors higher scores. Finally, worse patients than other types.ConclusionLactylation are involved malignancy formation. serves as promising biomarker patient prognosis efficacy.

Язык: Английский

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