Results 81 to 90 of about 68,671 (251)

A Non‐Canonical Core Transcriptional Regulatory Circuit Orchestrates Chromatin Reprogramming to Drive Osimertinib Resistance in Non‐Small Cell Lung Cancer

Advanced Science, EarlyView.
A non‐canonical core transcriptional regulatory circuit, composed of ID3, SMAD3, and NR2F2, drives Osimertinib resistance in non‐small cell lung cancer through super‐enhancer‐mediated activation of EPAS1, which couples neuroendocrine differentiation with ferroptosis evasion.
Aochu Liu, Zhenguo Liu, Lizhen Jiang, Andong Huang, Xinqing Lin, Xinyue Li, Bingyuan Liu, Shiwen Hu, Qiang Pan, Junjun Huang, Liyuan Yin, Liling Jiang, Wei Yi, Wenjun Mao, Yueyuan Zheng, Xianping Shi   +15 more
wiley   +1 more source

ProSiteHunter: A Unified Framework for Sequence‐Based Prediction of Protein‐Nucleic Acid and Protein‐Protein Binding Sites

Advanced Science, EarlyView.
This study proposed a unified sequence‐based framework for protein binding site prediction, which adopted a tri‐track semantic multi‐source feature fusion strategy to effectively capture diverse macromolecular interaction sites and further improved the accuracy of antibody‐antigen interaction prediction.
Dongliang Hou, Qihang Zhen, Zexin Lv, Xinyue Cui, Suhui Wang, Minghua Hou, Zhan Zhou, Xiaogen Zhou, Guijun Zhang   +8 more
wiley   +1 more source

A three-level regulatory mechanism of the aldo-keto reductase subfamily AKR12D

Nature Communications
Modulation of protein function through allosteric regulation is central in biology, but biomacromolecular systems involving multiple subunits and ligands may exhibit complex regulatory mechanisms at different levels, which remain poorly understood. Here,
Zhihong Xiao, Jinyin Zha, Xu Yang, Tingting Huang, Shuxin Huang, Qi Liu, Xiaozheng Wang, Jie Zhong, Jianting Zheng, Rubing Liang, Zixin Deng, Jian Zhang, Shuangjun Lin, Shaobo Dai   +13 more
doaj   +1 more source

A Brain‐Penetrant Nanobody Reveals GSK3β‐Driven Proline‐Directed Phosphorylation as a Master Regulator of Ischemic Neurodegeneration

Advanced Science, EarlyView.
A brain‐targeted nanoparticle enables delivery of a therapeutic nanobody (Nb.29E9) that inhibits pathogenic GSK3β signaling. This intervention restores AMPK/mTORC1/TGFβ homeostasis, attenuates neuroinflammation and oxidative stress, and promotes long‐term functional recovery after ischemic stroke.
Lan Li, Muyang Li, Lei Sun, Ying Yang, Yuanshun Wu, Ziyi Yin, Anni Wang, Peiyang Zhou, Shaoxiang Luo, Jian Chen, Jun Qin, Zhibing Ai, Zilong Yuan, Zhiqiang Dong, Min Zhang   +14 more
wiley   +1 more source

Allosteric Inhibition of Polycomb Repressive Complex 2 by an EZH2‐Selective Small Molecule Inhibitor

Advanced Science, EarlyView.
The study characterizes C36, a highly selective EZH2/PRC2 inhibitor that acts via a novel allosteric mechanism. Unlike previous inhibitors, C36 inhibits EZH2/PRC2 by disrupting the allosteric communication between EZH2 and EED in a SAM‐noncompetitive manner.
Ting Cao, Dongdong Liu, Haishan Gao, Chenyang Qin, Wen Zhang, Ziyun Lu, Dongxia Tan, Yuxiu Qu, Yusong Liu, Zhiran Zou, Hongtao Yu, Wei Qi   +11 more
wiley   +1 more source

A Phase‐Resolved Geometric Deep Learning Framework Maps Structural Determinants of Disease‐Associated Protein Aggregation and Guides Suppressor Design

Advanced Science, EarlyView.
SKALE 2.0 maps disease‐associated protein aggregation as a phase‐resolved structural process, linking mutation‐induced geometric perturbations to nucleation, elongation, and suppressor design. Across neurodegenerative proteins, the framework reveals cryptic aggregation vulnerabilities, separates phase‐concordant and phase‐switching mutations, and ...
Jia Shen Sio, Wei Xuan Wilson Loo, Yan Shan Loo, Wen Xin Tan, Hui Xuan Lim, Huitao Liu, Chen Seng Ng   +6 more
wiley   +1 more source

Probing the activity modification space of the cysteine peptidase cathepsin K with novel allosteric modifiers.

PLoS ONE, 2014
Targeting allosteric sites is gaining increasing recognition as a strategy for modulating the activity of enzymes, especially in drug design. Here we investigate the mechanisms of allosteric regulation of cathepsin K as a representative of cysteine ...
Marko Novinec, Brigita Lenarčič, Antonio Baici   +2 more
doaj   +1 more source

Conformational Transduction Amplification in a Biomimetic Polyelectrolyte for Ultrasensitive Imaging of Iron Metabolism

Advanced Science, EarlyView.
This work designs a peptide‐free polyelectrolyte with stable, switchable conformations and near‐infrared fluorescence in water. It harnesses a cooperative Fe3+‐triggered sheet‐to‐helix transition to generate nonlinear fluorescence quenching, enabling the ultrasensitive, real‐time visualization of Fe3+ ion distribution and metabolic trafficking at ...
Yeqiang Zhou, Danqi Yang, Yiwei Wang, Shuangyan Li, Fan Fan, Jiayu Zou, Cheng Zhang, Yang Liu, Hong Tan, Mingming Ding   +9 more
wiley   +1 more source

Functional Suppression of SCAP Triggers Endoplasmic Reticulum Stress‐Dependent Ferroptosis by Impairing Cholesterol Metabolism in Gastric Cancer

Advanced Science, EarlyView.
This study reveals a novel GC therapy targeting cholesterol homeostasis. Inhibiting the SCAP sterol‐sensing domain causes lethal ER stress via cholesterol accumulation, paradoxically forcing continuous synthesis that triggers ferroptosis. The findings link sterol sensing, metabolic dysregulation, and ferroptosis, establishing an anti‐cancer paradigm ...
Qianqian Xu, Guangzhao Pan, Lele Zhang, Xiangliu Chen, Kui Zhang, Yang Lu, Zibo Duan, Aiping Chen, Hailong Shen, Yuxi Zhang, Xiaowu Dong, Jinzhou Huang, Xing Huang, Kai Miao, Qian Hua, Fangfang Tao, Weidong Zhang, Jiang‐Jiang Qin   +17 more
wiley   +1 more source

Lactate‐Driven Restriction of Mitochondrial Permeability Transition Promotes Resistance to Chemo‐Immunotherapy by Suppressing Tumor PANoptosis

Advanced Science, EarlyView.
Tumor‐derived lactate establishes a metabolic lock that drives chemo‐immunotherapy resistance by suppressing PANoptosis. Mechanistically, KAT8 lactylates the mitochondrial translocator ANT2, which recruits PGAM5 to dephosphorylate CypD. This cascade restricts mitochondrial permeability transition pore opening, preventing pro‐inflammatory mtDNA leakage.
Sen Zhong, Wenlong Chen, Fanglong Liu, Shengyi Zhou, Bolin Yu, Yuying Wang, Xiqian Zhou, Xuehui Wang, Diya Liu, Zhuoyu Zhang, Xinran Wang, Mounia Lalouly, Yiwen Li, Zhefei Du, Tao Yan, Zhihui Xiao, Zhou Zhou, Huanhuan Zhu, Fengyuan Qian, Bowen Zheng, Lin Fang   +20 more
wiley   +1 more source