Results 31 to 40 of about 4,116 (175)

The TRIM33 Bromodomain Recognizes Histone Lysine Lactylation

ACS 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, Paul F. W. Sidlowski, Erica A. Steen, Sarah L. Wynia-Smith, Daniel J. Sprague, Robert F. Keyes, Brian C. Smith   +6 more
openaire   +2 more sources

Phosphorylation‐Facilitated CKB Lactylation At K11 By GCN5 Enhances Creatine Kinase Activity and Mitigates Neuronal Damage After Cerebral Ischemia‐Reperfusion

Advanced Science, EarlyView.
This study uncovers hierarchical coordination between K11 lactylation and S199 phosphorylation of CKB in cerebral ischemia‐reperfusion injury. Such dual modifications potentiate CKB enzymatic function, remodel energy metabolism, alleviate oxidative stress and neuronal damage, and represent a viable therapeutic target for stroke treatment.
Chao Duan, Ruolin Zhang, Shihui Ding, Ying Feng, Tao Shen, Ziwei Wang, Wendai Bao, Ke Shui, Jun Qin, Jun Chen, Min Zhang, Zijing Ren, Dongmei Zhao, Xingrong Guo, Zhibing Ai, Xin Yang, Peiyang Zhou, Zhiqiang Dong   +17 more
wiley   +1 more source

Histone Lactylation Antagonizes Senescence and Skeletal Muscle Aging by Modulating Aging‐Related Pathways

Advanced Science
Epigenetic alterations are among the prominent drivers of cellular senescence and/or aging, intricately orchestrating gene expression programs during these processes.
Fanju Meng, Jianuo He, Xuebin Zhang, Wencong Lyu, Ran Wei, Shiyi Wang, Zhehao Du, Haochen Wang, Jinlong Bi, Xueyang Hua, Chao Zhang, Yiting Guan, Guoliang Lyu, Xiao‐Li Tian, Lijun Zhang, Wenbing Xie, Wei Tao   +16 more
doaj   +1 more source

HNRNPU K181 Lactylation Drives Cervical Cancer Growth by Upregulating PHGDH and Reprogramming Serine Metabolism

Advanced Science, EarlyView.
Lactate in cervical cancer induces HNRNPU K181 lactylation, opposed by NAA50‐mediated acetylation and suppressed by Pazopanib. This lactylation enhances HNRNPU binding to PHGDH pre‐mRNA exon 1, maintaining exon 1‐containing transcripts and mRNA stability, thereby activating serine metabolism.
Chang Zhang, Qingfei Meng, Hui Jiao, Huixin Liu, Xiangchao Wang, Honglan Zhou, Yishu Wang   +6 more
wiley   +1 more source

β‐Elemene Rescues Radiation‐Induced Enteritis by Orchestrating a Host‐Microbiome Circuit That Fuels Epigenetic DNA Repair

Advanced Science, EarlyView.
This study elucidates that β‐elemene promotes cellular uptake of L. gasseri‐derived lactate by enhancing the membrane translocation of MCT1 in a CD147‐dependent manner. Intracellular lactate, through the lactylation of RBBP4 at the K26 site, recruits EP300 to the promoter regions of downstream genes (POLD1/POLD3), catalyzing H3K27ac modification.
Jiancheng He, Jiapeng Bao, Shukang Deng, Weijie Zang, Haoming Yan, Zihao Zhao, Guangze Zhang, Ruiqing Liu, Junjie Chen, Yilin Hu, Wanjiang Xue   +10 more
wiley   +1 more source

Unveiling Lactylation: A Novel Frontier in Cancer Stemness and Therapy

Advanced Science, EarlyView.
Tumor metabolism and epigenetic regulation are intrinsically linked. This review highlights lactylation as a pivotal bridge connecting these processes, acting as an active epigenetic effector in cancer stemness. We delineate how lactylation orchestrates the cancer stem cell landscape and evaluate its regulatory networks.
Ting Li, Hongyu Gu, Chang Liu, Yuesheng Lv, Feifei Li, Liang Liang, Jia Yi, Xuanyi Wang, Yi Zhun Zhu, Chuan Xu   +9 more
wiley   +1 more source

Epigenetic Silencing of RFX7 Defines a Transcriptional Axis Linking Lactate Metabolism to Immune Checkpoint Therapy in Glioblastoma

Advanced Science, EarlyView.
Glioblastoma (GBM) exhibits RFX7 silencing via promoter hypermethylation, which downregulates PIK3IP1 to activate PI3K/AKT signaling, increase lactate accumulation, and enhance histone H4K12 lactylation. This lactylation upregulates PD‐L1/CSF1 expression and drives the immunosuppressive microenvironment formation.
Liying Han, Jinpeng Zhou, Gang Zhu, Fan Chen, Leiyang Li, Wenxing Cui, Fang Sun, Tian Feng, Yue Zhang, Qiang Wang, Shuoyao Ma, Chengxuan Guo, Ziwen Zhang, Kai Wang, Jiahui Wang, Liangbo Wang, Wencong Li, Chenyi Yuan, Haixiao Liu, Liang Wang, Yan Qu   +20 more
wiley   +1 more source

Targeting Lactate‐Driven Stromal Autophagy via MCT1 Disrupts the Immunosuppressive Niche and Sensitizes Pancreatic Cancer to PD‐1 Blockade

Advanced Science, EarlyView.
Tumor‐derived lactate activates PSCs through MCT1‐mediated Vps34 lactylation and autophagy. These activated PSCs secrete CXCL9/10, upregulating PD‐1 on CD8+ T cells via the CXCR3/STAT3 axis to foster immunosuppression. Disrupting this metabolic crosstalk by targeting MCT1 effectively sensitizes pancreatic cancer to PD‐1 blockade, presenting a promising
Wenfeng Zhuo, Rong Hu, Yuhang Hu, Ping Hu, Shengbo Han, Guozheng Lv, Zhu Zeng, Yong Zhao, Yang Li, Yan Huang, Yingsong Zhao, Hongda Wang, Guangyu Zhao, Eryang Zhao, Gang Zhao   +14 more
wiley   +1 more source

Histone lactylation promotes rheumatoid arthritis progression by increasing NFATc2 expression and the production of anti-lactylated histone autoantibodies

Nature Communications
Elevated lactate in the joint microenvironment of rheumatoid arthritis patients is crucial for disease progression, though the mechanism remains unclear. This study shows significantly increased global lactylation levels within fibroblast-like synoviocytes from RA patients compared to healthy controls, with lactylated proteins being enriched in ...
Gan Wu, Chenglin Yang, Yuan Huang, Bin Liu, Haige Zhai, Zelin Cao, Siyue Lu, Jijian Ji, Xinyue Yin, Xianming Xin, Shengwei Jin, Youzhi Cai, Jianguang Wang   +12 more
openaire   +2 more sources

ANXA2+ Small Extracellular Vesicles Drive Chemoresistance in Anaplastic Thyroid Cancer by Promoting XRCC5 Lactylation and Enhancing Non‐Homologous End‐Joining Repair

Advanced Science, EarlyView.
ANXA2+ sEVs promote cisplatin resistance in ATC by stabilizing the SRC/LDHA interaction, increasing LDHA phosphorylation and activity, and lactate production. Elevated lactate levels promote KAT5‐mediated lactylation of XRCC5 at lysine 265, enhancing its binding to XRCC6.
Shanshan Su, YiShan Xiong, Yuxuan Liang, Xiang Min, Daofeng Dai   +4 more
wiley   +1 more source