Results 71 to 80 of about 37,458 (256)

PRMT1‐Mediated LDHA Methylation Drives STAT3 Lactylation to Orchestrate Intestinal Inflammation and Tumorigenesis

Advanced Science, EarlyView.
This study identifies an immunometabolic axis wherein SAM‐driven PRMT1 methylates LDHA, enhancing its activity. The resultant lactate induces STAT3 K709 lactylation, which stabilizes an active conformation to promote STAT3 phosphorylation and IL‐10 expression.
Hui Wang, Mengyu Zhang, Weipeng Gong, Jiaxuan Wu, Junping Zhang, Wenxiu Zhang, Yue Liu, Kui Wang, Canhua Huang, Jun Zhou, Sijin Wu, Yan Li, Tianliang Li   +12 more
wiley   +1 more source

Enhanced Glycolysis‐Driven Histone H3K18 Lactylation Regulates Epileptogenesis by Modulating the E3 Ubiquitin Ligase COP1

Advanced Science, EarlyView.
Neuronal PKM2‐driven glycolysis generates excess lactate that triggers histone H3K18 lactylation (H3K18la), establishing a pathogenic metabolic‐epigenetic axis in epilepsy. Elevated H3K18la enriches the Cop1 promoter, transcriptionally upregulating the E3 ubiquitin ligase COP1, which subsequently drives proteasomal degradation of GABAARβ2 and impairs ...
Yuan Meng, Yanlin Guo, Liumi Jiang, Jing Luo, Yan Liu, Ziwei Yuan, Pingyang Ke, Ran Duan, Fei Xiao   +8 more
wiley   +1 more source

Molecular mechanism of allosteric communication in Hsp70 revealed by molecular dynamics simulations.

PLoS Computational Biology, 2012
Investigating ligand-regulated allosteric coupling between protein domains is fundamental to understand cell-life regulation. The Hsp70 family of chaperones represents an example of proteins in which ATP binding and hydrolysis at the Nucleotide Binding ...
Federica Chiappori, Ivan Merelli, Giorgio Colombo, Luciano Milanesi, Giulia Morra   +4 more
doaj   +1 more source

GPCRs in CAR‐T Cell Immunotherapy: Expanding the Target Landscape and Enhancing Therapeutic Efficacy

Advanced Science, EarlyView.
Chimeric antigen receptor T cell therapy faces dual challenges of target scarcity and an immunosuppressive microenvironment in solid tumors. This review highlights how G protein‐coupled receptors can serve as both novel targets to expand the therapeutic scope and functional modules to enhance CAR‐T cell efficacy.
Zhuoqun Liu, Yuchen Xiao, Yamin Zhao, Lihe Dai, David J.H. Shih, Shikang Liang, Honglei Tian, Liu Liu, Feng Tian, Bing Liu, Lei Chang, Chao Zhang   +11 more
wiley   +1 more source

Autoimmune Encephalitis in Acute Care—Pathology, Diagnosis, and Management

Advanced Science, EarlyView.
ABSTRACT Autoimmune encephalitis (AE) is characterized by immune‐mediated inflammation of the brain parenchyma, presenting with various neurological syndromes, including but not limited to seizures, altered consciousness, neuropsychiatric symptoms, and movement disorders.
Suneesh Thilak, David Okoh, William Scotton, Shanika Samarasekera, Vikram Patil, Suresh Renukappa, Andrew Macduff, Subashini Suresh, Rajeev Krishnadas, Tonny Veenith   +9 more
wiley   +1 more source

Molecular Glue cc‐885 Inhibits VHL‐Deficient Clear Cell Renal Cell Carcinoma via ETS1 Degradation

Advanced Science, EarlyView.
VHL‐deficient kidney cancer lacks effective treatments. This study reveals that the molecular glue degrader cc‐885 hijacks the cellular recycling system to selectively destroy the oncogenic protein ETS1, effectively killing VHL‐mutant tumors. Combining CC‐885 with the approved drug belzutifan achieves powerful synergy, offering a promising new ...
Taowei Yang, Qihao Li, Kun Ye, Kezhi Liu, Mi Zhou, Minyu Chen, Lican Liao, Kangbo Huang, Zhu Wang, Qiong Deng, Jieyan Wang, Meiyu Jin, Xu Chen, Hui Liang, Jiaxing Zhang, Junhang Luo   +15 more
wiley   +1 more source

Dose‐Dependent Reprogramming of Chromatin Accessibility by SOX4 Drives the Transcriptional Response to Iron Overload

Advanced Science, EarlyView.
This study demonstrates that iron overload triggers widespread chromatin compaction and transcriptional repression in human granulosa cells, recapitulating features of endometriosis. The epigenetic reprogramming is orchestrated by a TFEB‐SOX4‐SWI/SNF axis, with SOX4 acting as a central, dosage‐sensitive regulator.
Feifei Li, Yaoqiu Wu, Guangyu Yang, Jingyi Lai, Xiaoyue Sun, Liyan Wang, Xiaoli Li, Jing Zhang, Qingxue Zhang, Hui Chen, Haiyan Lin, Bingxiang Xu, Junfeng Zhang, Hailong Wang, Anming Meng, Chunwei Cao   +15 more
wiley   +1 more source

Modulation of global low-frequency motions underlies allosteric regulation: demonstration in CRP/FNR family transcription factors.

PLoS Biology, 2013
Allostery is a fundamental process by which ligand binding to a protein alters its activity at a distinct site. There is growing evidence that allosteric cooperativity can be communicated by modulation of protein dynamics without conformational change ...
Thomas L Rodgers, Philip D Townsend, David Burnell, Matthew L Jones, Shane A Richards, Tom C B McLeish, Ehmke Pohl, Mark R Wilson, Martin J Cann   +8 more
doaj   +1 more source

Targeting Supramolecular Active Complexes of Nav1.7/Nav1.8 to Relieve Chronic Neuropathic Pain

Advanced Science, EarlyView.
In mice and patients with severe chronic neuropathic pain (NP), Nav1.7, Nav1.8, TrkB, and five cytoskeletal proteins form supramolecular active complexes (SMACs) with polygonal lattice structures as noxious signal amplifiers in dorsal root ganglion (DRG) neurons.
Liting Sun, Hang Xian, Yunxin Shi, Taotan Yang, Hongyan Shuai, Wenchao Hu, Siying Fei, Miao Xu, Taoyuan Yang, Ruilong Xia, Ting Wen, Fengting Zhu, Yan Fu, Yang Li, Wei Xia, Ran Qian, Yuanying Liu, Zhicheng Tian, Lamei Li, Qian Zhou, Lize Xiong, Rui Cong, Ceng Luo, Shengxi Wu, Xiafeng Shen, Xin Yu, Rou‐Gang Xie, Changgeng Peng   +27 more
wiley   +1 more source

Mechanistic Insights into the Mechanism of Allosteric Inhibition of Ubiquitin-Specific Protease 7 (USP7)

Biomolecules
Ubiquitin-specific protease 7 (USP7), a deubiquitinase enzyme responsible for removing ubiquitin (Ub) from target proteins, plays a crucial role in oncogenic pathways and has been implicated in various human diseases.
Xuebin Wang, Ning Liu, Nuan Li, Shaoyong Lu, Zongtao Chai   +4 more
doaj   +1 more source