The lactylation modification of proteins plays a critical role in tumor progression DOI Creative Commons

Dai Yi,

Ke Zhou,

Yu Pan

и другие.

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Март 19, 2025

Lactylation modifications have been shown to be a novel type of protein post-translational (PTMs), providing new perspective for understanding the interaction between cellular metabolic reprogramming and epigenetic regulation. Studies that lactylation plays an important role in occurrence, development, angiogenesis, invasion metastasis tumors. It can not only regulate phenotypic expression functional polarization immune cells, but also participate formation tumor drug resistance through variety molecular mechanisms. In this review, we review latest research progress modification tumors, focusing on its mechanism action cell regulation microenvironment (TME), resistance, aiming provide theoretical basis ideas discovery therapeutic targets methods. Through in-depth analysis modification, it is expected open up direction treatment potential strategies overcoming improving clinical efficacy.

Язык: Английский

Epigenetics-targeted drugs: current paradigms and future challenges DOI Creative Commons

Wanlin Dai,

Xinbo Qiao, Yuanyuan Fang

и другие.

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Язык: Английский

Процитировано

24
Hexokinase 2-mediated metabolic stress and inflammation burden of liver macrophages via histone lactylation in MASLD DOI Creative Commons
Jinyang Li, Xiancheng Chen, Shiyu Song

и другие.

Cell Reports, Год журнала: 2025, Номер 44(3), С. 115350 - 115350

Опубликована: Фев. 25, 2025

Язык: Английский

Процитировано

2
Insight into the roles of lactylation in macrophages: functions and clinical implications DOI

Min Shu,

Dingci Lu,

Ziyi Zhu

и другие.

Clinical Science, Год журнала: 2025, Номер 139(02), С. 151 - 169

Опубликована: Янв. 1, 2025

Lactylation, a post-translational modification, has been linked to gene transcription regulation through epigenetic modulation in various pathophysiological processes. The lactylation regulatory proteins, known as writers, erasers, and readers, govern their dynamics by adding, removing, recognizing lactyl groups on proteins. Macrophages, cells of the immune system, maintain homeostasis, responding dynamically diverse internal external stimuli. Emerging researches unveil that lactylation, inducing macrophage activation polarization, affects functionality pathological conditions such inflammation, tumor microenvironment, fibrosis. Evidence progressively indicates lactate-driven alterations levels within macrophages can influence pathogenesis numerous diseases. This review aims systematically summarize research progress macrophages, explore its functions mechanisms which contributes pathology different disease phenotypes, propose future directions along with potential diagnostic therapeutic strategies.

Язык: Английский

Процитировано

1
Lactylation in cancer: metabolic mechanism and therapeutic strategies DOI Creative Commons
Ying Sui, Ziyang Shen, Zhenling Wang

и другие.

Cell Death Discovery, Год журнала: 2025, Номер 11(1)

Опубликована: Фев. 20, 2025

Recent progress in cancer metabolism research has identified lactylation as a critical post-translational modification influencing tumor development and progression. The process relies on lactate accumulation the activation of lactate-sensitive acyltransferases. Beyond its role epigenetic regulation, emerged significant factor evolution, offering fresh opportunities for developing targeted therapies that transcend traditional approaches. This review explores growing importance biology highlights potential advancing diagnostic tools therapeutic strategies.

Язык: Английский

Процитировано

1
Histone lactylation stimulated upregulation of PSMD14 alleviates neuron PANoptosis through deubiquitinating PKM/PKM2 to activate PINK1-mediated mitophagy after traumatic brain injury DOI
Lei Xu,

Yangfan Ye,

Wei Gu

и другие.

Autophagy, Год журнала: 2025, Номер unknown, С. 1 - 19

Опубликована: Фев. 26, 2025

Alleviating the multiple types of programmed neuronal death caused by mechanical injury has been an impetus for designing neuro-therapeutical approaches after traumatic brain (TBI). The aim this study was to elucidate potential role PSMD14 (proteasome 26S subunit, non-ATPase 14) in neuron and specific mechanism through which it improves prognosis TBI patients. Here, we identified differential expression protein between controlled cortical impact (CCI) sham mouse groups LC-MS proteomic analysis found that significantly upregulated neurons qPCR western blot. suppressed stretch-induced PANoptosis improved motor ability learning performance CCI vivo. Mechanistically, PINK1 phosphorylation levels at Thr257 activated PINK1-mediated mitophagy deubiquitinating PKM/PKM2 (pyruvate kinase M1/2) maintain PKM stability. PSMD14-induced promoted mitochondrial homeostasis reduced ROS production, ultimately inhibited PANoptosis. upregulation due increase histone lactation modification level lactate treatment alleviated via increasing expression. Our findings suggest could be a therapeutic approach improving patients.Abbreviations: CCI: impact; CQ: chloroquine; DUBs: enzymes; H3K18la: H3 lysine 18 lactylation; IB: immunoblot; IHC: immunohistochemistry; IP: immunoprecipitation; MLKL: mixed lineage domain like pseudokinase; PI3K: phosphoinositide 3-kinase; PINK1: PTEN induced 1; PKM/PKM2: pyruvate M1/2; PSMD14: proteasome 14; ROS: reactive oxygen species; RIPK1: receptor interacting serine/threonine RIPK3: 3; TBI: injury.

Язык: Английский

Процитировано

1
Lactylation in cancer: Mechanisms in tumour biology and therapeutic potentials DOI Creative Commons
Yipeng He,

Tianbao Song,

Jinzhuo Ning

и другие.

Clinical and Translational Medicine, Год журнала: 2024, Номер 14(11)

Опубликована: Окт. 25, 2024

Lactylation, a recently identified form of protein post-translational modification (PTM), has emerged as key player in cancer biology. The Warburg effect, hallmark tumour metabolism, underscores the significance lactylation progression. By regulating gene transcription and function, facilitates metabolic reprogramming, enabling tumours to adapt nutrient limitations sustain rapid growth. Over past decade, extensive research revealed intricate regulatory network underlying tumours. Large-scale sequencing machine learning have confirmed widespread occurrence sites across proteome. Targeting enzymes or pathways demonstrated promising anti-tumour effects, highlighting therapeutic potential this modification. This review comprehensively explores mechanisms cells microenvironment. We expound on application advanced omics technologies for target identification data modelling within field. Additionally, we summarise existing anti-lactylation drugs discuss their clinical implications. providing comprehensive overview recent advancements, aims stimulate innovative accelerate translation lactylation-based therapies into practice. KEY POINTS: Lactylation significantly influences metabolism regulation, contributing Advanced reveal shows promise enhancing drug efficacy overcoming chemotherapy resistance. outlines implications future directions oncology.

Язык: Английский

Процитировано

5
The role of protein lactylation: A kaleidoscopic post-translational modification in cancer DOI Creative Commons
Marta Iozzo, Elisa Pardella, Elisa Giannoni

и другие.

Molecular Cell, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

The recently discovered lysine lactylation represents a critical post-translational modification with widespread implications in epigenetics and cancer biology. Initially identified on histones, has been also described non-histone proteins, playing pivotal role transcriptional activation, protein function, cellular processes. Two major sources of the lactyl moiety have currently distinguished: L-lactyl-CoA (precursor L-lactyl moiety) S-D-lactylglutathione D-lactyl moiety), which enable enzymatic non-enzymatic mechanisms lactylation, respectively. Although specific writers, erasers, readers this are still unclear, acetyltransferases deacetylases proposed as crucial mediators lactylation. Remarkably, exerts significant influence cancer-related pathways, thereby shaping behavior during malignant transformation metastatic cascade. Hence, recent insights into underscore its growing potential tumor biology, targeting is emerging opportunity for treatment.

Язык: Английский

Процитировано

0
Lactate: A key regulator of the immune response DOI Creative Commons
Alba Llibre,

Salih Kucuk,

Atrayee Gope

и другие.

Immunity, Год журнала: 2025, Номер 58(3), С. 535 - 554

Опубликована: Март 1, 2025

SummaryLactate, the end product of both anaerobic and aerobic glycolysis in proliferating growing cells—with latter process known as Warburg effect—is historically considered a mere waste cell tissue metabolism. However, research over past ten years has unveiled multifaceted functions lactate that critically shape impact cellular biology. Beyond serving fuel source, is now to influence gene expression through histone modification function signaling molecule impacts wide range activities. These properties have been particularly studied context adaptive innate immune responses. Here, we review diverse roles regulation system during homeostasis disease pathogenesis (including cancer, infection, cardiovascular diseases, autoimmunity). Furthermore, describe recently proposed therapeutic interventions for manipulating metabolism human diseases.

Язык: Английский

Процитировано

0
L- and D-Lactate: unveiling their hidden functions in disease and health DOI Creative Commons

Jianting Li,

Peng Ma, Zhizhen Liu

и другие.

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Март 12, 2025

Lactate, once considered a mere byproduct of anaerobic metabolism, is now recognized as critical signaling molecule with diverse roles in physiology and pathology. There are two stereoisomers lactate: L- D-lactate. Recent studies have shown that disruptions these lactate distinct effects on health disease. L-lactate central to glycolysis energy transfer through the Cori cycle but also acts dominant lactylation isomer induced by glycolysis, influencing metabolism cell survival. Although less studied, D-lactate linked metabolic disorders plays role mitochondrial dysfunction oxidative stress. This review focuses both examines their biosynthesis, transport, expanding physiological pathological processes, particularly functions cancer, immune regulation, inflammation, neurodegeneration other diseases. Finally, we assess therapeutic prospects targeting highlighting emerging strategies for intervention clinical settings. Our synthesizes current understanding D-lactate, offering insights into potential targets innovation.

Язык: Английский

Процитировано

0
Oxygen Glucose Deprivation-Induced Lactylation of H3K9 Contributes to M1 Polarization and Inflammation of Microglia Through TNF Pathway DOI Creative Commons
Lu He, Rui Yin, Weijian Hang

и другие.

Biomedicines, Год журнала: 2024, Номер 12(10), С. 2371 - 2371

Опубликована: Окт. 17, 2024

Hypoxia-induced M1 polarization of microglia and resultant inflammation take part in the damage caused by hypoxic-ischemic encephalopathy (HIE). Histone lactylation, a novel epigenetic modification where lactate is added to lysine residues, may play role HIE pathogenesis. This study investigates histone lactylation hypoxia-induced microglial inflammation, aiming provide insights for treatment.

Язык: Английский

Процитировано

4