Results 81 to 90 of about 81,932 (256)

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

The mechanism of allosteric inhibition of protein tyrosine phosphatase 1B.

PLoS ONE, 2014
As the prototypical member of the PTP family, protein tyrosine phosphatase 1B (PTP1B) is an attractive target for therapeutic interventions in type 2 diabetes.
Shuai Li, Jingmiao Zhang, Shaoyong Lu, Wenkang Huang, Lv Geng, Qiancheng Shen, Jian Zhang   +6 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

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

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

Kinsenoside Targets IDH1 to Restore Microglial Immune‐Metabolic Homeostasis for Alzheimer's Disease Therapy

Advanced Science, EarlyView.
Dysregulated TCA cycle contributes to Alzheimer's disease (AD) pathogenesis. Here, we show that microglial isocitrate dehydrogenase 1 (IDH1) is a critical driver. Elevated IDH1 disrupts citrate metabolism and mitochondrial function, exacerbating AD pathology.
Qianqian Li, Yajin Liao, Yan‐bo Zhao, Hongxing Wu, Tong Jin, Shuoshuo Li, Yuhan Liu, Peng Li, Songying Ouyang, Zekai Li, YuTing Xia, Qian Hua, Rui‐Yuan Pan, Zengqiang Yuan   +13 more
wiley   +1 more source

Identification of a Novel Inhibitory Allosteric Site in p38α

PLOS ONE, 2016
In the present study, we report the discovery of a novel allosteric inhibitory site for p38α, a subclass of the mitogen-activated protein kinases (MAPK) family. The putative site was discovered after inspection of the crystallographic structure of the p38α-MK2 complex.
Patricia Gomez-Gutierrez, Pedro M Campos, Miguel Vega, Juan J Perez   +3 more
openaire   +4 more sources

SDS‐CRISPR for Single‐Nucleotide Variant Detection

Advanced Science, EarlyView.
Structure‐disruption‐sensitive CRISPR (SDS‐CRISPR) converts structural instability into single‐nucleotide precision, thereby overcoming mismatch tolerance in canonical Cas12a and enabling versatile diagnostics across DNA, RNA, and microRNA targets. When applied to rapid IDH1 mutation detection for glioma genotyping and integrated with lateral‐flow ...
Xin Guan, Chong Guo, Jiongyu Zhang, Rui Yang, Yerramsetti Ramachandra, Chengyu Hou, Minjie Pei, Shuo Zhang, Kurt T. Schalper, Xingye Liu, Qian Wu, Ketan R. Bulsara, Changchun Liu   +12 more
wiley   +1 more source

Chemical, target, and bioactive properties of allosteric modulation.

PLoS Computational Biology, 2014
Allosteric modulators are ligands for proteins that exert their effects via a different binding site than the natural (orthosteric) ligand site and hence form a conceptually distinct class of ligands for a target of interest.
Gerard J P van Westen, Anna Gaulton, John P Overington   +2 more
doaj   +1 more source