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The Role of Histone Lactylation in Diseases and Intervention by Traditional Chinese Medicine

open access: yesShengwu huaxue yu shengwu wuli jinzhan
Histone lactylation is a recently identified post-translational modification, wherein lactate mediates the enzymatic addition of lactyl groups to lysine residues on histones.
ZHANG Xin   +3 more
doaj   +1 more source

Histone lactylation links metabolism and gene regulation [PDF]

open access: yesNature, 2019
Cells regulate gene expression in part through the chemical labelling of histone proteins. Discovery of a label derived from lactate molecules reveals a way in which cells link gene expression to nutrient metabolism. Lactylation is a newly discovered epigenetic modification.
Luke T. Izzo, Kathryn E. Wellen
openaire   +1 more source

The TRIM33 Bromodomain Recognizes Histone Lysine Lactylation

open access: yesACS Chemical Biology
Histone lysine lactylation (Kla) regulates inflammatory gene expression in activated macrophages and mediates the polarization of inflammatory (M1) to reparative (M2) macrophages. However, the molecular mechanisms and key protein players involved in Kla-mediated transcriptional changes are unknown.
Raymundo Nuñez   +6 more
openaire   +2 more sources

AARS1‐Mediated RUNX3 K193 Lactylation Enhances the Activation and Cytotoxicity of CD8+T Cells in Smoking‐Related Emphysema

open access: yesAdvanced Science, EarlyView.
Exposure to CS causes an elevation of AARS1 levels, which increases the levels of RUNX3 lactylation at the K193 site and increases protein levels of RUNX3 through inhibition of autolysosomal degradation. Elevated RUNX3 levels promote CD8+T cell activation and augment their cytotoxicity, which induces alveolar epithelial cell death and facilitates the ...
Ying Zhu   +12 more
wiley   +1 more source

Metabolic Reprogramming in Glioblastoma Stem Cells Promotes Radiation Resistance Through a H3K18la/USP30/MBOAT2 Axis

open access: yesAdvanced Science, EarlyView.
LDHA‐driven lactate production in mesenchymal glioma stem cells promotes p300‐dependent H3K18 lactylation, activates USP30 transcription, and stabilizes MBOAT2 to remodel phosphatidylethanolamines toward ferroptosis‐resistant PE‐MUFA species. Disrupting this metabolic–epigenetic–lipid circuit enhances ferroptosis and sensitizes glioblastoma to ...
Zong Miao   +13 more
wiley   +1 more source

EP300‐Mediated MTF1‐K218 Lactylation Buffers AR‐Driven Copper Overload to Suppress Cuproptosis in Castration‐Resistant Prostate Cancer

open access: yesAdvanced Science, EarlyView.
Androgen receptor (AR) drives copper accumulation in prostate cancer while inducing MTF1 to buffer copper toxicity. EP300‐mediated lactylation of MTF1 at K218 promotes its nuclear translocation and metallothionein expression, sequestering cytosolic copper and preventing mitochondrial cuproptosis.
Kai Li   +21 more
wiley   +1 more source

EBV‐Driven ODC1 Upregulation Enhances Polyamine Anabolism to Promote Viral Replication and Cisplatin Resistance in Nasopharyngeal Carcinoma

open access: yesAdvanced Science, EarlyView.
EBV‑BZLF1 initiates ODC1‑driven polyamine anabolism that correlates with poor clinical prognosis in nasopharyngeal carcinoma. The ODC1–spermidine axis promotes viral replication, cell proliferation and innate immune evasion. Pharmacological inhibition of ODC1 rescues cisplatin sensitivity, establishing ODC1 as a viable therapeutic target for EBV ...
Yueshuo Li   +9 more
wiley   +1 more source

Lactate‐Induced K370 Lactylation of STING Inhibits STING‐TBK1 Signaling and Dampens Anti‐Tumor Immunity

open access: yesAdvanced Science, EarlyView.
Lactate accumulation in glioblastoma drives lactylation of STING at lysine 370, a primate‐conserved residue. K370 lactylation weakens STING‐TBK1 binding, destabilizes STING, and disrupts ER‐to‐Golgi trafficking, blunting type I interferon signaling. LDHA inhibition reverses K370 lactylation and improves the antitumor efficacy of STING agonism combined ...
Yueyao Wu   +11 more
wiley   +1 more source

WTAP Transcriptional Suppression by KLF9 Drives Osteoclastogenesis via M6A‐Mediated Regulation of CSF1R Signaling in Estrogen‐Deficient Osteoporosis

open access: yesAdvanced Science, EarlyView.
Scheme of the KLF9/WTAP/YTHDF2/m6A/CSF1R regulatory axis in osteoclastogenesis and estrogen‐deficient osteoporosis. WTAP‐mediated m6A modification of Csf1r mRNA governs osteoclastogenesis via a YTHDF2‐mediated pathway. Pathological upregulation of KLF9 drives Wtap transcription, leading to increased m6A deposition on the 3’‐UTR of Csf1r mRNA.
Chen Shen   +14 more
wiley   +1 more source

p300‐Mediated H3K18 Lactylation Drives Radiation‐Induced Pulmonary Fibrosis via VIRMA‐Dependent m6A Modification of GATA3

open access: yesAdvanced Science, EarlyView.
Radiation triggers glycolytic reprogramming in alveolar epithelial type II cells, causing pathological lactate accumulation. This metabolic stress drives p300‐mediated H3K18 lactylation at the VIRMA promoter, activating transcription. Elevated VIRMA enriches m6A on GATA3 mRNA, which YTHDF1 stabilizes, ultimately driving epithelial–mesenchymal ...
Junxuan Yi   +8 more
wiley   +1 more source

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