Results 121 to 130 of about 81,380 (309)

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

Reduced Maintenance DNA Methylation Thresholds Enable Sensitive Reporter Assays for UHRF1 and DNMT1 Inhibition

Advanced Science, EarlyView.
The authors engineer colorectal cancer cells with reduced redundancy of UHRF1 and DNMT1, key DNA methylation maintenance factors, lowering the maintenance threshold and sensitizing cells to inhibition. They develop reporter assays driven by endogenous tumor‐suppressor gene promoters with enhanced sensitivity and dynamic range to demethylating drugs ...
Cuicui Xia, Ying Cui, Jiongliang Wang, Wenjing Bai, Danyang Wang, Yao Chen, Huahui Guo, Liangyi Zong, Bing Qin, Xintong Cai, Jie Wang, Jing Huang, Scott B. Rothbart, Zufeng Guo, Stephen B. Baylin, Xiangqian Kong   +15 more
wiley   +1 more source

NUP85 Mediates Endoplasmic Reticulum Stress through the USP47/ASK1 Signaling Pathway to Regulate the Progression of Liver Fibrosis

Advanced Science, EarlyView.
In the present study, we have demonstrated that the NUP85‐USP47‐ASK1 signaling pathway may have regulated the progression of liver fibrosis through modulating ERS. Additionally, we have developed a CREKA‐coupled liposome to target delivery of MV, a pharmacological inhibitor of NUP85, to activated HSCs, thereby attenuating liver fibrosis. ABSTRACT Liver
Dashuai Yang, Haoran Yang, Linxin Pan, Chang Tian, Fucheng Zuo, Shilei Huang, Xianrui Li, Ming Chen, Cheng Qian, Jie Wang, Zhaolin Chen, Tao Xu   +11 more
wiley   +1 more source

Molecular Glue cc‐885 Inhibits VHL‐Deficient Clear Cell Renal Cell Carcinoma via ETS1 Degradation

Advanced Science, EarlyView.
VHL‐deficient kidney cancer lacks effective treatments. This study reveals that the molecular glue degrader cc‐885 hijacks the cellular recycling system to selectively destroy the oncogenic protein ETS1, effectively killing VHL‐mutant tumors. Combining CC‐885 with the approved drug belzutifan achieves powerful synergy, offering a promising new ...
Taowei Yang, Qihao Li, Kun Ye, Kezhi Liu, Mi Zhou, Minyu Chen, Lican Liao, Kangbo Huang, Zhu Wang, Qiong Deng, Jieyan Wang, Meiyu Jin, Xu Chen, Hui Liang, Jiaxing Zhang, Junhang Luo   +15 more
wiley   +1 more source

Functional characterization of Cullin-1-RING ubiquitin ligase (CRL1) complex in Leishmania infantum.

PLoS Pathogens
Cullin-1-RING ubiquitin ligases (CRL1) or SCF1 (SKP1-CUL1-RBX1) E3 ubiquitin ligases are the largest and most extensively investigated class of E3 ligases in mammals that regulate fundamental processes, such as the cell cycle and proliferation.
Camila Rolemberg Santana Travaglini Berti de Correia, Caroline Torres, Ellen Gomes, Giovana Maffei Rodriguez, Wesley Klaysson Pereira Regatieri, Nayore Tamie Takamiya, Luana Aparecida Rogerio, Iran Malavazi, Marcelo Damário Gomes, Jeziel Dener Damasceno, Vitor Luiz da Silva, Marcos Antonio Fernandes de Oliveira, Marcelo Santos da Silva, Alessandro Silva Nascimento, Adriano Cappellazzo Coelho, Sandra Regina Maruyama, Felipe Roberti Teixeira   +16 more
doaj   +1 more source

PSMA8‐Containing 20S Proteasome Regulates Spermiogenesis and Male Fertility

Advanced Science, EarlyView.
PSMA8 assembles s20S proteasome that degrades specific substrates in elongating spermatids. Degradation of s20S‐substrates activates translation of FXR1‐target mRNAs, which are essential for mitochondrial sheath formation and sperm morphogenesis.
Huiwen Cao, Qianting Zhang, Wei Xu, Anxuan Fang, Haomang Xu, Cheng Qiu, Lugeng He, Chao Yu   +7 more
wiley   +1 more source

Ecological Adaptation Mechanisms Underlying Successful Plant Reproduction

Advanced Science, EarlyView.
During floral induction, various environmental and endogenous signals converge to regulate the florigen protein, which is transported from leaves to the SAM to initiate flowering. Within the SAM, a complex network of receptor kinases and small peptides orchestrates floral development with high spatiotemporal precision.
Hang Zhao, Shenghui Huo, Yue Xing, Shuxin Zhang, Guilin Li, Yihui Liu, Chongyang Jin, Fuguang Li, Xiaoyang Ge   +8 more
wiley   +1 more source

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