Results 121 to 130 of about 197,780 (305)

Glutamine Deprivation Triggers Tribbles Homolog 3 Dependent G‐Quadruplex Resolution to Maintain DNA Repair and Tumor Survival

Advanced Science, EarlyView.
Glutamine deprivation triggers transient DNA damage yet activates adaptive repair in hepatocellular carcinoma cells. We identify TRIB3 as a stress‐induced nuclear scaffold that associates with DDX5 and G‐quadruplex DNA atBRCA1 andRAD51AP1 promoters. TRIB3 loss increases G4 accumulation, suppresses HR gene transcription, elevates γ‐H2A.X, and sensitizes
Qiang Ji, Xuedan Sun, Zhangran Sun, Mengfan Li, Xinyu Cheng, Shuai Tian, Rick F. Thorne, Jinming Li, Guangzhi Liu, Mian Wu, Xiaoying Liu   +10 more
wiley   +1 more source

The ITGB2‐COPS3‐SOX2 Axis and SOX2 Liquid‐Liquid Phase Separation: Dual Mechanisms Governing Osteosarcoma Stemness

Advanced Science, EarlyView.
Osteosarcoma stemness is driven by the ITGB2‐COPS3‐SOX2 signaling axis. This study reveals that nuclear COPS3 stabilizes SOX2, which in turn undergoes liquid‐liquid phase separation to promote stemness. Based on this mechanism, a novel COPS3 inhibitor, Z‐5891, was developed, effectively suppressing tumor growth and stemness in vivo, offering a ...
Lei Guo, Zhiqing Zhao, Wei Wang, Jianfang Niu, Bing Wang, Yunfei Lin, Wei Guo, Taiqiang Yan   +7 more
wiley   +1 more source

Plant Genetic Engineering: Technological Pathways, Application Scenarios, and Future Directions

Advanced Science, EarlyView.
This review maps the fast‐evolving landscape of plant genetic engineering, linking enabling platforms with trait‐focused applications in architecture optimization, stress resilience, yield improvement, and quality enhancement. It highlights how genome editing, transgenic strategies, and emerging multi‐gene approaches reshape breeding pipelines, while ...
Peilin Wang, Wenzhi Wang, Dongjiao Wang, Qibin Wu, Youxiong Que   +4 more
wiley   +1 more source

Cuproptosis and Mitophagy Mediated by the THUMPD1/IGF2R‐Dependent Suppression of AKT and Activation of AMPK Signaling Suppress Lung Adenocarcinoma Progression

Advanced Science, EarlyView.
THUMPD1 drives a tumor‐suppressive signaling cascade in lung adenocarcinoma by promoting IGF2R expression. IGF2R associates with PPP2R1A to suppress AKT and activate AMPK, leading to SLC31A1 upregulation and copper accumulation. Elevated copper disrupts mitochondrial metabolism and induces excessive mitophagy, thereby restraining tumor growth and ...
Kai Wu, Bo Qin, Zhuoyu Gu, Weizheng Ding, Xiaoming Chen, Kaishang Zhang, Yujin Qiao, Shuang Yuan, Song Zhao, Xiangnan Li, Peng Zhang   +10 more
wiley   +1 more source

E3 ubiquitin ligases: structural diversity, dysregulation in disease, and their emerging role in targeted therapeutic strategies

Frontiers in Molecular Biosciences
The Ubiquitin-Proteasome System (UPS) is a key mechanism of cellular homeostasis. A central part of this mechanism is E3 ubiquitin ligases, which selectively direct proteins to be ubiquitinated for degradation via the UPS.
Srineevas Sriram, Prahalad Krishnakumar, C. Sudandiradoss   +2 more
doaj   +1 more source

CRL4BDCAF11 E3 ligase targets p21 for degradation to control cell cycle progression in human osteosarcoma cells

Scientific Reports, 2017
Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells.
Zhi Chen, Kun Wang, Canglong Hou, Kaibiao Jiang, Bin Chen, Jianwei Chen, Lifeng Lao, Lie Qian, Guibin Zhong, Zude Liu, Caiguo Zhang, Hongxing Shen   +11 more
doaj   +1 more source

ZSL Orchestrates Synaptonemal Complex Assembly as a Central Region Scaffold to Ensure Synapsis Fidelity and Crossover Control in Polyploid Meiosis

Advanced Science, EarlyView.
A central molecular adaptor, ZSL, is identified that links transverse filaments ZYP1 to central element SCEP1/2 to drive synaptonemal complex assembly in Brassica napus. Loss of ZSL abolishes synaptonemal complex formation, disrupts meiotic chromosome segregation, and markedly increases crossovers, providing mechanistic insight into meiotic fidelity ...
Miaowei Geng, Shaochen Jia, Fei Cao, Cuiping Liu, Heshuang Zhang, Gang Xu, Jixin Zhuang, Yashi Zhang, Can Liu, Yuhang Zhao, Zilin Guo, Xinjie Yuan, Jiaqing Yang, Lei Chu, Bowei Cai, Hu Zhao, Chao Yang   +16 more
wiley   +1 more source

Identification of suitable target/E3 ligase pairs for PROTAC development using a rapamycin-induced proximity assay (RiPA)

eLife
The development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than
Bikash Adhikari, Katharina Schneider, Mathias Diebold, Christoph Sotriffer, Elmar Wolf   +4 more
doaj   +1 more source

A conserved ubiquitin ligase of the nuclear envelope/endoplasmic reticulum that functions in both ER-associated and Mat a2 repressor degradation [PDF]

, 2001
Substrate discrimination in the ubiquitin–proteasome system is believed to be dictated by specific combinations of ubiquitin–protein ligases (E3s) and ubiquitin-conjugating enzymes (E2s).
Swanson, Rob
core   +2 more sources

First Generation Proteolysis Targeting Chimeras (PROTACs) for the Treatment of Progeria

Advanced Science, EarlyView.
We report the first PROTACs designed to degrade progerin, introducing a novel therapeutic approach for progeria. The best compound, UCM‐18142, significantly reduces progerin levels and improves key disease phenotypes in patient‐derived cells and in the LmnaG609G/G609G mouse model, paving the way for new treatment strategies targeting the root cause of ...
Jon Macicior‐Michelena, Marcelino Telechea, Daniel Fernández, Alba García‐Martín, Ángeles Canales, Silvia Ortega‐Gutiérrez   +5 more
wiley   +1 more source