Results 101 to 110 of about 107,234 (254)

Harnessing MDM2‐Mediated Targeted Degradation of Transcriptional and Epigenetic Machinery to Disrupt Oncogenic Addictions in Pediatric Sarcoma

Advanced Science, EarlyView.
MDM2 dependency in pediatric sarcomas is driven by a novel p53‐independent oncogenic cistrome alongside canonical p53 pathway suppression. This study introduces MDM2‐recruiting transcriptional and epigenetic machinery degraders (MDM2‐TEMADs) as a novel precision oncology modality.
Jiawei Zhou, Xian Guan, Nan Li, Ying Zhang, Long Xie, Xingze Huang, Zhipeng Zhu, Zhuolin Ren, Xiaoyan Yu, Hanjun Guo, Yuanfang Wu, Lin Ma, Suya Zheng, Jingyao Zhang, Jiyang Liu, Victor Kuanmin Lee, Wenhao Chen, H. Phillip Koeffler, Jinhu Wang, Xin Han, Ye Chen, Liang Xu   +21 more
wiley   +1 more source

Dual Cytoplasmic and Chloroplastic Mechanisms Fine‐Tune Chloroplast Division through ARC3 Protein Stability

Advanced Science, EarlyView.
ARC3 levels are controlled by cytosolic and chloroplast proteolytic systems. PUB52 mediates ARC3 precursor ubiquitination and degradation in the cytosol, while CLPC1 promotes ARC3 degradation in chloroplasts, where ARC2 protects ARC3 from excessive breakdown. Disrupting these components causes chloroplast division defects, placing them upstream of ARC3.
Yang Yuan, Denghao Xiang, Ruiying Li, Zhichuang Yue, Zhipeng Wang, Honghong Hu   +5 more
wiley   +1 more source

FUCA2 Sustains AKT Signaling and Suppresses Senescence by Antagonizing FUT3‐Mediated ErbB3 Fucosylation in Lung Adenocarcinoma

Advanced Science, EarlyView.
ABSTRACT While targeted therapies have improved outcomes in lung adenocarcinoma (LUAD), many patients still lack targetable mutations. Here, we identified alpha‐L‐fucosidase 2 (FUCA2) as a crucial driver of LUAD by preventing cellular senescence. Mechanistically, through the restriction of fucosyltransferase 3 (FUT3)‐mediated α‐1,3‐fucosylation of ...
Lu Chen, Jintao Guo, Fei Li, Mingjie Gao, Runyang Li, Zhaozhang Huang, Yaolin Zheng, Chunyi Gao, Jihuan Hou, Qiang Yu, Bowen Zheng, Xuemei Chen, Wenqing Zhang, Xiaoting Hong, Yali Zheng, Daxuan Wang, Qiyuan Li, Tianhui Hu, Yan‐yan Zhan   +18 more
wiley   +1 more source

DTX3L Inhibits the EMT, Metastasis, and Stem‐Like Features of Gastric Cancer Through Promoting GSK‐3β Dependent SNAI1 Decay

Advanced Science, EarlyView.
This research identifies DTX3L as a critical tumor suppressor that inhibits epithelial‐mesenchymal transition (EMT), invasion and metastasis in gastric cancer. By functioning as an E3 ubiquitin ligase, DTX3L targets the master EMT regulator SNAI1 for GSK‐3β‐dependent proteasomal degradation.
Yang Chen, Zhen Li, Jiajia Shen, Jingyu Lin, Xiaoli Zhao, Rui Zhang, Ying Han, Zhen Wang   +7 more
wiley   +1 more source

Materials‐Guided Gene‐Ionizable Lipid Nanoparticles to Reverse Iron‐Associated Immune Resistance in Renal Cancer

Advanced Science, EarlyView.
ABSTRACT Iron overload is a common metabolic disturbance in cancer and contributes to poor outcomes in renal cell carcinoma (RCC), yet its effects on the tumour immune microenvironment remain unclear. Here we identify a previously unrecognized immunosuppressive axis in which iron overload downregulates the palmitoyltransferase ZDHHC12 in CD8+ T cells ...
Xin Jin, Yulong Hong, Chengliang Yin, Wanyang Guo, Yaxuan Wang, Ruijiang Zeng, Ruilin Liu, Zexian Ding, Xinlin Liu, Shangqing Ren, Qiyang Liang, Yaohui Wang, Xu Zhang, João Conde, Yuan Li, Xin Ma, Liangyou Gu   +16 more
wiley   +1 more source

Decoding the Mechanism of Action of a Parasite TGFβ Antagonist Inspires the Creation of Cell‐Type‐Specific TGFβ Modulators

Advanced Science, EarlyView.
The mammalian TGFβ interacts with ubiquitously expressed TGFBR1 and TGFBR2, and current TGFβ‐targeting agents are non‐cell‐selective. The cooperative interaction of the modular parasite TGFβ antagonist with multiple host (co‐)receptors empowers the design of TGM chimeras and bispecific antibodies that activate or inhibit TGFβ signaling in a cell ...
Maarten van Dinther, Tristin Schwartze, Jiying Zhang, Kun Fan, Gerard van der Zon, Luke Power, Cynthia S. Hinck, Claire Ciancia, Ananya Mukundan, Roman Gonzalez‐Prieto, Peter van Veelen, Rick M. Maizels, Andrew P. Hinck, Peter ten Dijke   +13 more
wiley   +1 more source

Mechanosensitive Piezo1/Osteocalcin/Irisin Axis Protects Against Disuse‐Induced Muscle Atrophy

Advanced Science, EarlyView.
Mechanical unloading suppresses bone Piezo1 expression, which reduces circulating undercarboxylated osteocalcin (unOCN). unOCN reduction subsequently exacerbates IMM‐induced Fndc5/Irisin decrease and drives severe muscle atrophy. Bone Piezo1 activation or exogenous osteocalcin/Irisin ameliorate muscle atrophy, while muscle‐specific Gprc6a or Fndc5 ...
Zhaolu Wang, Xiuying Jiang, Xi Sun, Hao Chen, Jianjun Jin, Xin'e Shi   +5 more
wiley   +1 more source

Cancer‐Associated Fibroblast‐Derived Sphingosine‐1‐Phosphate Activates a MALL–SDC4 Axis to Facilitate Perineural Invasion in Pancreatic Cancer

Advanced Science, EarlyView.
CAF‐derived S1P activates the S1PR3‐JNK‐Jun signaling pathway, thereby transcriptionally upregulating MALL expression in cancer cells. MALL increases the cell‐surface abundance of SDC4 by promoting its recycling and restricting its lysosomal degradation, which in turn enhances RhoA‐p‐MLC2‐dependent amoeboid invasion and SDC4‐PTN axis‐mediated cancer ...
Wang Peng, Mengdie Cao, Hai Huang, Shuya Bai, Luyao Liu, Jingwen Liang, Haochen Cui, Qiaodan Zhou, Shiru Chen, Jiamei Jiang, Luoxia Liu, Zhou Luan, Wei Chen, Si Xiong, Ronghua Wang, Bin Cheng, Yuchong Zhao   +16 more
wiley   +1 more source

New Insights for Polyphenolic Compounds as Naturally Inspired Proteasome Inhibitors. [PDF]

Pharmaceuticals (Basel), 2023
Marchese E, Gallo Cantafio ME, Ambrosio FA, Torcasio R, Valentino I, Trapasso F, Viglietto G, Alcaro S, Costa G, Amodio N.   +9 more
europepmc   +1 more source

Caveolin‐1 Stabilizes SERCA2 to Counteract Acute Kidney Injury via Suppression of Ca2+‐Dependent Endoplasmic Reticulum Stress in Distal Tubules

Advanced Science, EarlyView.
In AKI, initial kidney injury upregulates the expression of Cav‐1, which subsequently binds to and stabilizes SERCA2 via its scaffolding domain and through deubiquitination, thereby regulating Ca2+ homeostasis and ER stress. Conversely, Cav‐1 deficiency accelerates SERCA2 degradation, triggering Ca2+ overload and ER stress, and ultimately exacerbating ...
Yan Zhang, Xin He, Hao Huang, Rong Lu, Xin Lv, Shenglan Li, Sijue Zou, Jiawei Cheng, Yiwei Xiong, Zhenghao Deng, Qiongjing Yuan, Yanyun Xie, Ling Huang, Jiaxi Pu, Shao Liu, Qianbin Li, Jie Meng, Huixiang Yang, Lijian Tao, Zhangzhe Peng   +19 more
wiley   +1 more source