Results 51 to 60 of about 31,611 (205)

Heat Shock Protein 90: From Molecular Chaperone Function to Therapeutic Targeting in Malignancies

Advanced Science, EarlyView.
In this review, an integrated conceptual framework linking HSP90's molecular chaperone functions to its pathological roles in cancer is proposed. HSP90 serves as a central node that integrates oncogenic signaling, buffers proteotoxic stress, maintains cancer stem cell plasticity, and shapes tumor‐immune interactions, all of which converge to drive ...
Beibei Zhang, Xinxin Zou, Jiansong Zhou, Qinmiao Sun, Dahua Chen   +4 more
wiley   +1 more source

Chemically Regulated STING‐Activating Prodrugs of Deoxyribose Cyclic Dinucleotides Elicit Robust Immune Activation and Durable Antitumor Immunity

Angewandte Chemie, EarlyView.
All three diastereoisomers of an esterase‐sensitive phosphotriester dCDN prodrug demonstrate improved activity. The (Rp,Rp) diastereoisomer shows the highest activity with an EC50 of 1.7 nM in STING activation and displays the most pronounced antitumor activity via intravenous administration, significantly suppressing tumor proliferation, extending the
Zhiqiang Xie, Huimin Liu, Yuchen Yang, Xiaohan Sun, Jingwen Wang, Tianxiang Liu, Baifan Wang, Wenrui Qiu, Yiwen Sun, Yuting Bai, Yao Zhang, Dejun Ma, Rong Xiang, Shibo Li, Zhen Xi   +14 more
wiley   +2 more sources

NMI Regulates Adipose Adaptive Thermogenesis Through TLR4/IRF3 Signaling to Promote Obesity

Advanced Science, EarlyView.
Adipose tissue‐derived NMI is secreted under metabolic stress and suppresses adaptive thermogenesis through TLR4/IRF3 signaling, repressing the PPARα/PGC‐1α/UCP1 thermogenic transcriptional program. Genetic ablation or anti ‐ NMI monoclonal antibody treatment enhances energy expenditure, protects against DIO, and ameliorates adipose tissue inflammation,
Ting‐Ting Li, Xin‐Yuan Zhao, Min Zhang, Zhuang‐Feng Weng, Xiao‐Ran Guo, Ying‐Fang Liu, Qiao‐Ping Wang, Huan‐Huan Liang   +7 more
wiley   +1 more source

A Novel Transcript Isoform of TBK1 Negatively Regulates Type I IFN Production by Promoting Proteasomal Degradation of TBK1 and Lysosomal Degradation of IRF3

Frontiers in Immunology, 2020
TANK-binding kinase 1 (TBK1), an IKK-related serine/threonine kinase, is pivotal for the induction of antiviral type I interferon (IFN) by TLR and RLR signaling pathways.
Jie Zhang, Xiao Man Wu, Yi Wei Hu, Yi Wei Hu, Ming Xian Chang, Ming Xian Chang, Ming Xian Chang   +6 more
doaj   +1 more source

Intrinsically Mitochondria‐Targeting Nanozyme via Coordination‐Assembly of Natural Quercetin for Cascade Antioxidant Therapy of Cerebral Ischemia‐Reperfusion Injury

Advanced Science, EarlyView.
This study uncovers that quercetin naturally targets mitochondria. By coordinating quercetin with Fe3+, we engineer an ultrasmall cascade nanozyme (MCN) with superoxide dismutase‐catalase activities. MCN crosses the damaged blood–brain barrier, scavenges mitochondrial ROS, prevents mitochondrial DNA leakage, and blocks the cGAS‐STING pathway, thereby ...
Wenxuan Zheng, Zhicheng Wang, Xin Zhou, Shuya Wang, Xiaojing Shi, Tingli Xiong, Ruishi Li, Yuting Lin, Zhen Chen, Jiawen Wei, Fei Li, Jinwen Ge, Kelong Ai, Chong Liu, Guiming Deng   +14 more
wiley   +1 more source

p300 Degradation by the p53‐SIAH1 Axis Relieves TBK1 Acetylation to Enhance Innate Antiviral Immunity

Advanced Science, EarlyView.
This study identifies p300 as the acetyltransferase that acetylates TBK1 and inhibits its phosphorylation. Activation of the p53‐SIAH1 axis by immune response downregulates p300 expression to sustain innate antiviral immunity. Conditional p300 knockout in alveolar epithelial cells in vivo promotes antiviral responses and suppresses virus replication ...
Huidi Yu, Zhihao Zhan, Xiaoxiang Pan, Xinyue Zhang, Penggang Liu, Jing Sun, Xiulong Xu   +6 more
wiley   +1 more source

Pivotal role for the ESCRT-II complex subunit EAP30/SNF8 in IRF3-dependent innate antiviral defense.

PLoS Pathogens, 2017
The activation of interferon (IFN)-regulatory factor-3 (IRF3), characterized by phosphorylation and nuclear translocation of the latent transcription factor, is central to initiating innate antiviral responses.
Kattareeya Kumthip, Darong Yang, Nan L Li, Yunzhi Zhang, Meiyun Fan, Aarti Sethuraman, Kui Li   +6 more
doaj   +1 more source

Radiation‐Induced Tumor‐Intrinsic LTβR N‐Glycosylation Suppresses Pyroptosis Through TRIM28‐Mediated PCBP2 SUMOylation to Promote Gastric Cancer Radioresistance

Advanced Science, EarlyView.
Radiotherapy triggers LTβR N‐glycosylation, enhancing its overall protein stability and nuclear retention. This accumulation drives TRIM28‐mediated PCBP2 SUMOylation, suppressing pyroptosis and conferring gastric cancer radioresistance. Therapeutically, a targeted nanoplatform (cRGD‐Lipo@EMD) effectively disrupts this regulatory axis, offering a highly
Weijie Zang, Yunlong Ji, Chunwang Zhou, Xiwen Li, Zhuang Lu, Guangze Zhang, Yu Chen, Wanjiang Xue, Yilin Hu   +8 more
wiley   +1 more source

Pathogen specific, IRF3-dependent signaling and innate resistance to human kidney infection.

PLoS Pathogens, 2010
The mucosal immune system identifies and fights invading pathogens, while allowing non-pathogenic organisms to persist. Mechanisms of pathogen/non-pathogen discrimination are poorly understood, as is the contribution of human genetic variation in disease
Hans Fischer, Nataliya Lutay, Bryndís Ragnarsdóttir, Manisha Yadav, Klas Jönsson, Alexander Urbano, Ahmed Al Hadad, Sebastian Rämisch, Petter Storm, Ulrich Dobrindt, Ellaine Salvador, Diana Karpman, Ulf Jodal, Catharina Svanborg   +13 more
doaj   +1 more source

RNA‐Binding Protein RBM25 Targets the mRNA Stability of GTPase Rab22a to Restrict Viral Entry and Infection

Advanced Science, EarlyView.
This study identifies RNA‐binding protein RBM25 as a broad‐spectrum antiviral factor acting independently of type I interferon. It blocks viral entry by suppressing GTPase Rab22a via the RC3H1‐mediated destabilization of Rab22a mRNA. Viral downregulation of RBM25 enhances GTPase Rab22a expression and viral entry, revealing an unreported post ...
Yingying Ding, Huiying Chen, Yuyu Jiang, Chunyan Zhao, Jie Bai, Yan Xiang, Zeting Wang, Xixi Wang, Bing Rui, Wanda Tang, Yue Ding, Zhenzhen Zhan, Yunkai Zhang, Xingguang Liu   +13 more
wiley   +1 more source