Results 121 to 130 of about 162,141 (238)

Antagonistic Ubiquitin Switching by USP7 and RNF40 Orchestrates KDM6A Homeostasis to License Coronavirus Susceptibility

Advanced Science, EarlyView.
We identify an antagonistic ubiquitin circuit that controls cellular permissiveness to multiple coronaviruses. The deubiquitinase USP7 stabilizes the epigenetic regulator KDM6A to upregulate viral receptors, while the E3 ligase RNF40 degrades KDM6A by catalyzing K6/K11‐ubiquitin chains of KDM6A for autophagic degradation.
Meng‐Zhuo Huang, Zhong‐Yuan Yang, Shi Wang, Yan Ge, Lan Lin, Mia Madel Alfajaro, Renata B. Filler, Wan‐Yao Song, Ming‐Zhu Kong, Jin Wei   +9 more
wiley   +1 more source

Potent and Selective IGF‐IIR‐Recruiting Bifunctional Molecules for Targeted Lysosomal Degradation of Extracellular and Membrane Proteins

Advanced Science, EarlyView.
Lysosome‐targeting chimeras (LYTACs) enable degradation of extracellular and membrane proteins via lysosomal trafficking. We report a novel IGF‐II mutant (Del1–7, Y27L) that selectively engages IGF‐IIR while avoiding IGF‐IR and IR‐A. mutIGF‐II–based LYTACs enhance target internalization and degradation and support a genetically encodable, all‐protein ...
Yuan Zhao, Yaxian Liao, Pengyun Li, Regina Stasser de Gonzalez, Xuankun Chen, Nicholas S. Nieto, Florence M. Brunel, Nick Cox, Joseph Stock, Matthew McHenry, Guangsen Fu, Penghsuan Huang, Wenxin Wu, Deqin Cai, Lingjun Li, Alexander N. Zaykov, Weiping Tang   +16 more
wiley   +1 more source

Involvement of the Ubiquitin-Proteasome System in the Formation of Experimental Postsurgical Peritoneal Adhesions

Mediators of Inflammation, 2012
We investigated the Ubiquitin-Proteasome System (UPS), major nonlysosomal intracellular protein degradation system, in the genesis of experimental postsurgical peritoneal adhesions.
Clara Di Filippo, Pasquale Petronella, Fulvio Freda, Marco Scorzelli, Marco Ferretti, Sivestro Canonico, Francesco Rossi, Michele D'Amico   +7 more
doaj   +1 more source

Chaperone‐Mediated Autophagic Degradation of USP9X in Macrophages Exacerbates Postmyocardial Infarction Inflammation and Cardiac Dysfunction

Advanced Science, EarlyView.
This study demonstrates that inflammatory stimuli induce the acetylation‐triggered, chaperone‐mediated autophagic degradation of ubiquitin‐specific peptidase 9 X‐linked (USP9X) in macrophages. USP9X acts as a macrophage “inflammation switch” after myocardial infarction (MI). USP9X loss destabilizes tumor necrosis factor receptor‐associated factor (TRAF)
Biqing Wang, Xiangheng Cai, Mengqi Li, Xue Liu, Junhui Xue, Ye Liu, Ding Ai, Xinyang Hu   +7 more
wiley   +1 more source

Targeted Mitochondrial ECSIT Overexpression Attenuates MASH by Increasing OTUD3 Expression

Advanced Science, EarlyView.
Mitochondrial ECSIT expression is reduced during MASH pathogenesis. Overexpression of mitochondrial ECSIT mitigates steatohepatitis and maintains hepatic metabolic homeostasis. Mechanistically, ECSIT enhances intramitochondrial OTUD3 expression to stabilize SIRT3 through deubiquitination, thus preserving mitochondrial function and impeding disease ...
Yuqing Jiang, Tingting Tong, Pengxi Shi, Xiaofan Chen, Chenhao Wang, Qingyuan Weng, Sihan Chen, Linli Que, Qi Chen, Yuehua Li, Qiang Zhu, Jiantao Li   +11 more
wiley   +1 more source

Elevated TRIM25 Impairs Poly (ADP‐ribose) Metabolism via PARG Degradation and Mediates Compression‐Induced Intervertebral Disc Degeneration

Advanced Science, EarlyView.
TRIM25 acts as a multifunctional hub driving intervertebral disc degeneration under mechanical stress. Mechanical compression significantly upregulates TRIM25 expression, establishing it as a key E3 ubiquitin ligase platform. TRIM25 targets PARG and Ku80 via distinct molecular interfaces, triggering their ubiquitination and degradation.
Zhangrong Cheng, Haiyang Gao, Wenbo Wu, Pengzhi Shi, Xianglong Chen, Zimu Yu, Wang Wu, Kangcheng Zhao, Cao Yang, Yukun Zhang   +9 more
wiley   +1 more source

The Role of Ubiquitination and Deubiquitination in the Pathogenesis of Acute Kidney Injury: Progress in Research

Biomedicines
Acute kidney injury (AKI) remains a critical clinical challenge due to its complex pathophysiology and lack of targeted therapies. We hypothesize that the ubiquitin-proteasome system (UPS) and ubiquitin-like modifiers (UBLs) are not merely isolated ...
Yu Zhou, Shuchun Tao, Lei Liu, Lei Zhang
doaj   +1 more source

Cortical Somatostatin Neurons Regulate Seizure Susceptibility via MINAR1/Gαs–cAMP Signaling

Advanced Science, EarlyView.
Our study identifies MINAR1 as a novel regulator of cortical interneuron excitability and seizure susceptibility. MINAR1 is preferentially expressed in SST+ interneurons. Genetic ablation of MINAR1 leads to seizure hypersensitivity, reduced SST+ neuron excitability, and impaired Gαs–cAMP signaling, disrupting the E/I balance.
Wei‐Tang Liu, Zhi‐Bin Hu, Ling Hu, Yu‐Bing Wang, Qiong Zhang, Ning‐Ning Song, Xi‐Yue Liu, Jia‐Yin Chen, Hong‐Wen Zhu, Bing‐Yao Zhou, Yun‐Chao Tao, Li Zhao, Ze‐Xuan Li, Yi‐Wei Li, Jia‐Qi Chen, Si‐Xin Tu, Cong‐Cong Qi, Sai‐Dan Ding, Gang Peng, Lin Xu, Yu‐Qiang Ding   +20 more
wiley   +1 more source

Microglial GPR35 Ameliorates Epileptogenesis and Neuroinflammation via PDGFA Domain 2 Signaling

Advanced Science, EarlyView.
Activation of microglial G protein–coupled receptor 35 (GPR35) by L‐kynurenic acid (L‐Kyna) initiates a platelet‐derived growth factor A (PDGFA)–dependent phosphoinositide 3‐kinase–protein kinase B (PI3K–AKT) signaling cascade that dampens hippocampal neuroinflammation, thereby restraining epileptogenesis, lowering seizure susceptibility, and ...
Qi Wang, Tingting Qu, Qibing Sun, Ran Li, Junfei Dong, Yuming Du, Ziyin Xuan, Lei Wang, Hanli Li, Jianyun Sun, Fangliang Chen, Jinshuai Liu, Zifan Yang, Jianxiang Lei, Qian Yang, Bin Wang, Zhiming Zhou, Yu Wang   +17 more
wiley   +1 more source

Xanthatin Targets CISD1 to Drive Ferroptosis and Mitophagy as a Dual Anticancer Strategy in Triple‐Negative Breast Cancer

Advanced Science, EarlyView.
Triple‐negative breast cancer has a poor prognosis. Xanthatin directly targets and degrades CISD1, triggering ferroptosis through iron dysregulation. The concurrently activated mitophagy synergistically amplifies ferroptotic cell death. Xanthatin also demonstrates potent in vivo anti‐tumor efficacy with minimal toxicity, highlighting its therapeutic ...
Qinwen Liu, Haojie Chen, Xiang Li, Jingxin Liu, Yiwen Li, Zhenyi Shi, Shenshen Guo, Qingfeng Du, Aiping Lu, Daogang Guan   +9 more
wiley   +1 more source