Results 71 to 80 of about 504,547 (295)

Natural Product Toosendanin Suppresses the Malignant Development of Skin Melanoma by Targeting BNC2 for Degradation

Advanced Science, EarlyView.
BNC2 exhibits context‐dependent opposing functions across multiple cancer types. This study reveals BNC2 as an oncogenic driver of melanoma proliferation and metastasis through transcriptional activation of PIK3CA. The natural compound TSN simultaneously degrades BNC2 and its oncogenic partner SMAD3 via CRBN‐dependent ubiquitination.
Hui Dai, Xin Mei Zhang, Jing Cheng Zhang, Xu Ting Deng, Qiao Liu, Mustafa Hussein Ali, Fang Zhou Yin, Wu Yin   +7 more
wiley   +1 more source

Ligand-induced Conformational Plasticity of the CTLH E3 Ligase Receptor GID4

ChemMedChem
ABSTRACT The application of targeted protein degradation (TPD) is currently constrained by the limited availability of low-molecular-weight molecules that can recruit E3 ligases other than CRBN (Cereblon) or VHL (Von Hippel-Lindau ligase).
Daria Kotlarek, Katarzyna Dudek, Bartosz Woźniak, Martyna W. Pastok, Dmitrii Shishov, Sylvain Cottens, Michał Biśta, Emilia Krzywiecka, Karolina M. Górecka‐Minakowska, Kinga Jurczak, Tomáš Drmota, Justyna Adamczyk, Szymon Faliński, Daria Gajewska, Marta Klejnot, Aleksandra Król, Monika Cuprych‐Belter, Iwona Mames, Arnaud Mathieu, Aleksandra Podkówka, Ziemowit Pokładek, Kamil Przytulski, Alicja N. Skowron, Magdalena Sypień, Anna Szlachcic, Toshimitsu Takagi, Weronika Wanat, Igor H. Wierzbicki, Janusz Wiśniewski, Michał J. Walczak   +29 more
openaire   +2 more sources

Liganded ERα Stimulates the E3 Ubiquitin Ligase Activity of UBE3C to Facilitate Cell Proliferation [PDF]

Molecular Endocrinology, 2015
Abstract Estrogen receptor (ER)α is a well-characterized ligand-dependent transcription factor. However, the global picture of its nongenomic functions remains to be illustrated. Here, we demonstrate a novel function of ERα during mitosis that facilitates estrogen-dependent cell proliferation.
Maiko, Okada, Fumiaki, Ohtake, Hiroyuki, Nishikawa, Wenwen, Wu, Yasushi, Saeki, Keiji, Takana, Tomohiko, Ohta   +6 more
openaire   +2 more sources

Pharmacophore-Based Machine Learning Model To Predict Ligand Selectivity for E3 Ligase Binders

ACS Omega, 2023
E3 ligases are enzymes that play a critical role in ubiquitin-mediated protein degradation and are involved in various cellular processes. Pharmacophore analysis is a useful approach for predicting E3 ligase binding selectivity, which involves identifying key chemical features necessary for a ligand to interact with a specific protein target cavity ...
Reagon Karki, Yojana Gadiya, Philip Gribbon, Andrea Zaliani   +3 more
openaire   +2 more sources

Multi‐Technique Integration Identifies O‐GlcNAc Transferase in Fibroblast‐Like Synoviocytes as a Therapeutic Target for Rheumatoid Arthritis

Advanced Science, EarlyView.
AI‑guided single‑cell transcriptomics identifies OGT as a key regulator enriched in rheumatoid arthritis fibroblast‑like synoviocytes (RA‐FLSs). Inflammatory stimuli activate the OGT–SAP130 axis, which modulates the H3K27ac/H3K27me3 balance and epigenetically silences BTG2, promoting aggressive transformation of RA‑FLSs.
Duoli Xie, Jie Huang, Chunhao Cao, Zhenchao Tang, Xingchen Li, Jianmin Guo, Xinxin Chen, Fang Wang, Dongyi He, Jie Li, Yu Du, Bing He, Jianhua Yao, Aiping Lu, Chao Liang   +14 more
wiley   +1 more source

Cysteine-reactive covalent chloro-N-acetamide ligands induce ferroptosis mediated cell death

EMBO Reports
Covalent inhibitors are an attractive targeting strategy that has expanded the development of degraders to target poorly druggable proteins including the E3 ligase RNF4. We show that RNF4 is a potential vulnerability of AML.
Gina Gotthardt, Janik Weckesser, Georg Tascher, Sara Barros da Gama, Hannah J Uckelmann, Shibo Sun, Martin P Schwalm, Thorsten Mosler, Giulio Ferrario, José Pedro Friedmann Angeli, Christian Münch, Stefan Knapp, Stefan Müller   +12 more
doaj   +1 more source

Chemotherapy‐Activated GSK3β‐DNMT1 Signaling Upregulates CD47 to Evade Macrophage Phagocytosis and Drive Temozolomide Resistance in Glioblastoma

Advanced Science, EarlyView.
Temozolomide treatment activates GSK3β, driving DNMT1 phosphorylation, destabilization, and CD47 promoter hypomethylation in glioblastoma. This epigenetic shift upregulates CD47, enabling TMZ‐treated GBM cells to evade macrophage phagocytosis, survive chemotherapy, and acquire resistance.
Jie Li, Shuai Ying, Yi Zhang, Jingjing Wang, Quan Wan, Lingli Gong, Daxing Xu, Zhenkun Yang, Hongnian Lu, Ying Yin, Xiangming Fang, Zhening Pu   +11 more
wiley   +1 more source

Single‐Molecule Imaging of Endogenous RNA Using a Miniaturized and Circularly Permuted CRISPR‐Cas13 Degron‐Masking System CDegSR

Advanced Science, EarlyView.
CDegSR, a new tool for imaging RNA at single molecule level in living cells was developed by researchers. Background noise was eliminated by protein engineering and making it degrade when not bound to its target. This allowed individual RNA molecules to be clearly imaged and tracked.
Shipeng Shao, Hongchen Zhang
wiley   +1 more source

Identification of novel 7-hydroxycoumarin derivatives as ELOC binders with potential to modulate CRL2 complex formation

Scientific Reports
The VHL-containing cullin-RING E3 ubiquitin ligase (CRL2VHL) complex is an E3 ligase commonly used in targeted protein degradation (TPD). Hydroxyproline-based ligands that mimic VHL substrates have been developed as anchor molecules for proteolysis ...
Yonghyeok Kim, Seon Jeong Baek, Eun-Kyung Yoon, Minhee Choi, Jung-Hoon Kim, Kyungtae Kim, Chi Hoon Park, Byung Il Lee   +7 more
doaj   +1 more source

Basal Autophagy Is Necessary for A Pharmacologic PPARα Transactivation

Cells, 2022
Autophagy is a conserved cellular process of catabolism leading to nutrient recycling upon starvation and maintaining tissue and energy homeostasis. Tissue-specific loss of core-autophagy-related genes often triggers diverse diseases, including cancer ...
Eun Young Kim, Jae Man Lee
doaj   +1 more source