Results 121 to 130 of about 211,577 (291)

Discovery of SKP2‐Recruiting PROTACs for Target Protein Degradation

Advanced Science, EarlyView.
Based on the SKP2‐targeting ligand SL1, we designed non‐covalent PROTACs by linking it with the BRD4 inhibitor JQ1 and the AR antagonist AL through a linker. These PROTACs successfully induced the ubiquitination of BRD4 and AR, followed by proteasome‐mediated degradation.
Guanjun Dong, Aima Huang, Ziqing Zhao, Bikai Lai, Xin Pan, Huiyu Yang, Xiaohan Xu, Tianwei Wang, Fangchen Zhao, Zhimin Zhang, Yongbo Xue, Guanjun Deng, Wenbin Deng, Jianwei Chen   +13 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

Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy

Advanced Science, EarlyView.
Lactate, once deemed a metabolic waste, emerges as a central regulator of cancer progression. This review elucidates how lactate and its epigenetic derivative, protein lactylation, orchestrate tumor metabolism, immune suppression, and therapeutic resistance.
Jiajing Gong, Yuhang Xie, Zhijie Weng, Yongzhi Wu, Longjiang Li, Bo Li   +5 more
wiley   +1 more source

An Insulin‐Exosome‐TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer

Advanced Science, EarlyView.
In pancreatic ductal adenocarcinoma (PDAC), insulin is associated with activation of PI3K/AKT–RAB3A signaling and enhanced secretion of TNFAIP8‐enriched exosomes from tumor cells. Uptake of these exosomes by fibroblasts is linked to TRIM21‐dependent STAT1 degradation and the emergence of myofibroblastic CAF–associated features, accompanied by increased
Zhenyu Li, Li Chen, Tao Wang, Haiyang Jiang, Huijuan Wang, Mengyu Li, Guanpeng Xie, Chunhua Xi, Han Yan, Chunhui Lu, Chenchen Li, Hanyu Zhu, Feihu Sun, Lingdi Yin, Jun Yu, Yi Miao   +15 more
wiley   +1 more source

Single‐Cell Transcriptomics Reveals FLS2‐Dependent Hypoxia Signaling and ERF13‐Mediated Transcription During flg22‐Triggered Immunity

Advanced Science, EarlyView.
This study employs sc‐RNA sequencing, genetics, and phenotyping to systematically map the cell‐type‐specific immune responses triggered by flg22. It reveals FLS2‐dependent transcriptional reprogramming in epidermal and mesophyll cells, and uncovers crosstalk between immune and hypoxia signaling pathways.
Yaping Zhou, Aizhi Qin, Mengfan Li, Qianli Zhao, Luyao Kong, Lulu Yan, Chunyang Li, Hao Liu, Yinpeng Zhang, Jiani Long, Mengyu Liao, Mengmeng Zhou, Xiaoli Fan, Baozhen Wang, Wenxuan Kang, Shui Wang, Zhixin Liu, Xuwu Sun   +17 more
wiley   +1 more source

Oxidative Stress Sensor Keap1 Functions as an Adaptor for Cul3-Based E3 Ligase To Regulate Proteasomal Degradation of Nrf2

Molecular and Cellular Biology, 2004
A. Kobayashi, Moon-Il Kang, H. Okawa, Makiko Ohtsuji, Y. Zenke, T. Chiba, K. Igarashi, Masayuki Yamamoto   +7 more
semanticscholar   +1 more source

USP35 Acts as a Deubiquitinating Enzyme for ID3 to Promote Immune Escape in Colorectal Cancer

Advanced Science, EarlyView.
USP35 stabilizes ID3 expression by deubiquitinating the K2/K30 site, thereby upregulating PD‐L1 and promoting immune escape in colorectal cancer. IU1, an inhibitor of USP35 enzyme activity, has been shown to inhibit USP35, thereby accelerating ID3 degradation, enhancing CD8+ T cell killing, and reversing the immunosuppressive microenvironment ...
Wenxin Chen, Ling Wang, Hongmei Fan, Lisheng Li, Lingyu Zhang, Ruoxin Li, Fang Liu, Fuli Wen, Yunbin Ye, Chuanzhong Huang   +9 more
wiley   +1 more source

Recent Advances in the Development of Pro-PROTAC for Selective Protein Degradation

Pharmaceutics
PROTACs are trimeric small molecules consisting of a specific modulator of the target protein connected to a ligase-recruiting ligand via a suitably flexible linker.
Fady Hakem, Ahmad Abdelwaly, Reem Alshaman, Abdullah Alattar, Fawaz E. Alanazi, Sawsan A. Zaitone, Mohamed A. Helal   +6 more
doaj   +1 more source

F‐Box and Leucine‐Rich Repeat Protein 4 (FBXL4) Maintains Sarcomere Integrity and Cardiac Function by Enhancing K48‐Linked Ubiquitinated Degradation of Profilin‐1 (PFN1)

Advanced Science, EarlyView.
Schematic diagram depicting the proposed signaling mechanisms underlying the effects of FBXL4 in the setting of cardiac hypertrophy. Under hypertrophic stimulation, cardiomyocytes‐specific overexpression FBXL4 maintains sarcomere integrity and cardiac function by enhancing K48‐linked ubiquitinated degradation of PFN1 at the K70 site.
Xingda Li, Xueqi He, Xinyuan Hao, Yu Zhang, Xin Zhao, Shuang Wang, Zhenru Wang, Haonan Du, Hongda Li, Lian Yi, Zhimin Du, Weijie Du   +11 more
wiley   +1 more source

β‐Adrenergic Signaling Promotes Anti‐Tumor Immunity in TP53‐mutant Oral Squamous Cell Carcinoma

Advanced Science, EarlyView.
β‐adrenergic stimulation enhances anti‐tumor immunity in TP53‐deficient oral squamous cell carcinoma by inducing tumor‐derived secretion of CXCL10, which attracts and activates cytotoxic CD8+ T cells. The findings demonstrate that β‐adrenergic signaling alters tumor–immune interactions via CXCL10‐mediated paracrine activation, revealing a neuro‐immune ...
Frederico O. Gleber‐Netto, Deborah Silverman, Tongxin Xie, Shamima Akhter, Nicole R. Vaughn, Adewale Adebayo, Kala Chand Debnath, Shorook Naara, Shajedul Islam, Erik Knutsen, Emily Lorin Ashkin, Simone Anfossi, Sara Leahey, Patrick Hwu, Sebastien Talbot, Erica K Sloan, Robert Saddawi‐Konefka, Roberto Rangel, Jeffrey N. Myers, George A. Calin, Moran Amit   +20 more
wiley   +1 more source