Results 41 to 50 of about 7,774 (200)

SOX5 Orchestrates Malignant Evolution via Promoter‐Centric Chromatin Remodeling in MYC‐Driven B‐Cell Lymphoma

Advanced Science, EarlyView.
In MYC‐enforced B‐cell lymphoma, SOX5 occupies promoter‐proximal regulatory regions and is associated with reduced chromatin accessibility at the PCNP locus. PCNP repression promotes proliferative remodeling by limiting apoptosis and cell‐cycle restraint.
Yiyou Mao, Zhenyuan Jia, Xiao‐Qin Mu, Ruilin Wang, Jianli Ma, Qingyuan Zhang, Yuwei Deng   +6 more
wiley   +1 more source

Targeted Degradation of Picornaviral 3C Protease via PROTACs Confers High Barrier to Viral Resistance and Broad‐Spectrum Antiviral Activity

Advanced Science, EarlyView.
This study reports D34 as the first PROTAC degrader that targets the 3C protease of picornaviruses. D34 effectively degrades EV71 3C protease via the ubiquitin‐proteasome pathway. More importantly, D34 exhibits a high resistance barrier and shows broad‐spectrum antiviral activity against multiple picornaviruses, highlighting its potential as a novel ...
Weilong Deng, Junyu Chen, Yingyue Pang, Yuanyuan Zhang, Siqian Chen, Guoliang You, Xiaoman Tian, Zhongxin Xu, Jing Wang, Luqing Shang   +9 more
wiley   +1 more source

The Potential of Proteolytic Chimeras as Pharmacological Tools and Therapeutic Agents

Molecules, 2020
The induction of protein degradation in a highly selective and efficient way by means of druggable molecules is known as targeted protein degradation (TPD).
Bernat Coll-Martínez, Antonio Delgado, Bernat Crosas   +2 more
doaj   +1 more source

A Second Pathogenic Protein, PolyGN2C‐iso2, Reveals a Dual‐Protein Pathology in Neuronal Intranuclear Inclusion Disease

Advanced Science, EarlyView.
This study reveals that NOTCH2NLC transcript variant 2 generates PolyGN2C‐iso2, an aggregating protein present within intranuclear inclusions of NIID patient tissues. A novel mouse model expressing PolyGN2C‐iso2 recapitulates white matter abnormalities and cognitive deficits, mechanistically linked to mitochondrial dysfunction. These findings support a
Kang Zhang, Wenhao Ma, Yi Zhou, Zhijie Wu, Pan Gao, Hongze Niu, Hongfei Tai, Tianyi Zhao, Zheyue Dong, Li Li, Yan Zhang, An Wang, Si Shen, Yueyang Li, Sifei Yu, Yan Peng, Wang Sheng, Xiaoyan Dong, Hua Pan, Kaibin Shi, Magdalena J. Koziol, Xiaobing Wu, Zaiqiang Zhang   +22 more
wiley   +1 more source

Trafficking Deficiency of TMEM175 Variants in Parkinson's Disease Pathogenesis and the Prospects of Precision Medicine

Advanced Science, EarlyView.
This study identifies that the PD‐associated TMEM175‐L156P variant disrupts lysosomal ion channel trafficking by causing aberrant endoplasmic reticulum retention. A “chaperone–agonist” bifunctional small molecule restores TMEM175‐L156P lysosomal localization and channel function, thereby alleviating PD‐relevant cellular phenotypes and highlighting a ...
Ting Luo, Yu He, Shuyao Li, Haoyu Guan, Ruili Cui, Yu Shi, Zhongwen Jiang, Siyu Wang, Xuan Li, Jiyuan Li, Mei Hu, Yupeng Zhou, Beisha Tang, Yanyan Zhang, Zhaobing Gao, Yu Zhou, Zhenhua Liu, Ping Li   +17 more
wiley   +1 more source

A Single‐Amino‐Acid Ligand for LAT1: A Minimalist and Modular Platform for Lysosome‐Targeted Degradation of Membrane Proteins

Advanced Science, EarlyView.
LA‐LYTAC repurposes the cancer‐enriched amino acid transporter LAT1 as a lysosomal trafficking receptor for targeted membrane‐protein degradation. A single phenylalanine‐derived ligand, modularly linked to antibodies or small‐molecule binders, recruits PD‐L1, EGFR, or integrins to LAT1, triggering transporter‐mediated internalization, lysosomal ...
Liquan Zhu, Ke Liu, Haotian Liu, Chaoqi He, Xiaozhen Liu, Xin Zeng, Misha Mao, Yuxiao Mu, Ying Li, Qinghui Zheng, Hongchao Tang, Da Qian, Xuli Meng   +12 more
wiley   +1 more source

A Small‐Molecule DEPTAC Rescues Cognitive Deficits by Targeted Dephosphorylation of Pathological Tau

Advanced Science, EarlyView.
TP2 is a fully synthetic small‐molecule dephosphorylation‐targeting chimera that recruits endogenous PP2A‐Bα to Tau, enabling targeted removal of pathological phosphate modifications. In two tauopathy mouse models, systemic TP2 reduces Tau pathology, preserves neuronal and synaptic integrity, improves neuroimmune homeostasis, and rescues cognition ...
Fei Sun, Yang Liu, Qiuzhi Zhou, Qingyuan Hu, Weixia Wang, Yue Xiao, Jingfen Su, Guanting Liu, Miaomiao Sun, Lixia Chen, Hua Li, Ying Yang, Jian‐Zhi Wang   +12 more
wiley   +1 more source

Ubiquitous regulation of cerebrovascular diseases by ubiquitin‐modifying enzymes

Clinical and Translational Medicine
Cerebrovascular diseases (CVDs) are a major threat to global health. Elucidation of the molecular mechanisms underlying the pathology of CVDs is critical for the development of efficacious preventative and therapeutic approaches.
Jingyong Huang, Zhenhu Zhu, Dirk Schlüter, Kate Lykke Lambertsen, Weihong Song, Xu Wang   +5 more
doaj   +1 more source

PROTAC‐Engineered Protein/DNA Nanoantigen is a Potent Booster for Dendritic Cell Vaccines in Cancer Immunotherapy

Advanced Science, EarlyView.
A PROTAC‐functionalized protein/DNA‐integrated nanoantigen platform is developed to enhance dendritic cell vaccine potency. By combining a VHL‐recruiting peptide‐modified antigen with a sustained expression plasmid within CaCO3 nanoparticles, this system amplifies cross‐presentation, promotes DC maturation, and elicits robust Th1 and CTL responses ...
Peng Liu, Qiang Chen, Zhe Zhou, Yuekang Xu, Jinyao Li   +4 more
wiley   +1 more source

Improving Proteolysis‐Targeting Chimera Delivery by Targeting Key Biomarkers in Tumor Endocytosis Pathways

MedComm – Biomaterials and Applications
Proteolysis‐targeting chimeras (PROTACs) are promising therapeutic agents for targeted protein degradation via the ubiquitin‐proteasome system; however, their clinical application is severely constrained by poor membrane permeability due to high ...
Huahua Chen, Jiayan Jiao, Huiling Yang, Tao He   +3 more
doaj   +1 more source