Results 91 to 100 of about 38,040 (251)

Intrinsic disorder within an AKAP-protein kinase A complex guides local substrate phosphorylation

eLife, 2013
Anchoring proteins sequester kinases with their substrates to locally disseminate intracellular signals and avert indiscriminate transmission of these responses throughout the cell.
F Donelson Smith, Steve L Reichow, Jessica L Esseltine, Dan Shi, Lorene K Langeberg, John D Scott, Tamir Gonen   +6 more
doaj   +1 more source

Master Regulator SMC1A, Stabilized by N6‐Methyladenosine Reader IGF2BP1, Promotes HCC Progression Through Facilitating Enhancer–Promoter Interaction of Nestin

Advanced Science, EarlyView.
IGF2BP1‐mediated m6A stabilization sustains SMC1A expression, enabling cohesin‐associated chromatin regulation of Nestin in hepatocellular carcinoma. This work reveals an epitranscriptomic‐chromatin‐cytoskeletal regulatory axis linked to malignant phenotypes and identifies SMC1A as a biologically relevant vulnerability in HCC.
Zhenxiang Peng, Diguang Wen, Lu Zeng, Lin Lv, Shengtao Liao, Wenguang Zhang, Zhechuan Mei, Chuanfei Li   +7 more
wiley   +1 more source

Diffusion‐Based Generative Model With Scaffold‐Hopping Strategy Yields Highly Potent Bioactive Molecules

Advanced Science, EarlyView.
SMarT‐Diff introduces a multi‐objective generative paradigm that integrates scaffold hopping with structure‐aware scoring to enable controlled exploration beyond the training distribution. The framework consistently balances drug‐likeness, synthesizes accessibility and bioactivity, yielding chemically diverse candidates with enhanced properties.
Yuwei Yang, Xiaoqing Gong, Shukai Gu, Jing Li, Bo Liu, Yanan Tian, Qianqian Zhang, Xiaojun Yao, Huanxiang Liu   +8 more
wiley   +1 more source

Aptamer‐Targeted PrPC Drives Colorectal Cancer Metastasis via a LYN‐STAT3 Complex and Enables Liquid Biopsy Detection

Advanced Science, EarlyView.
The aptamer WHY‐3E identifies PrPC as a CRC driver. Stabilized by USP18, endocytosed PrPC forms a LYN/STAT3 complex, upregulating MSN transcription to promote metastasis. Crucially, WHY‐3E sensitively detects PrPC‐positive circulating exosomes, establishing a robust theoretical foundation for non‐invasive clinical diagnostics.
Chunlin Wang, Hongyu Wu, Chaojing Zheng, Hao Zhang, Xiaoqiu Wu, Jiaqi Wang, Zewen Chang, Jun Xiang, Yunxiao Liu, Chenkai Zhang, Yuliuming Wang, Hao Jiang, Yuchen Zhong, Jun Luo, Ying Chen, NaNa Zhang, Weiyuan Zhang, Ziming Yuan, ChaoXia Zou, Weihong Tan, Meng Wang, Hanqing Hu, Tao Bing, Guiyu Wang   +23 more
wiley   +1 more source

Molecular basis of AKAP79 regulation by calmodulin

Nature Communications, 2017
The A-kinase anchoring protein AKAP79 is regulated by calmodulin (CaM). Here, the authors use crosslinking coupled to mass spectrometry to identify the CaM-binding site in AKAP79 and present the structure of CaM bound to an AKAP79 peptide.
Neha Patel, Florian Stengel, Ruedi Aebersold, Matthew G. Gold   +3 more
doaj   +1 more source

SuFEx‐Enabled Reprogramming of Flavonoids for Selective α‐Glucosidase Covalent Inhibition

Advanced Science, EarlyView.
Selective inhibition of intestinal α‐glucosidase remains limited by poor enzyme specificity and off‐target metabolic effects. Here, SuFEx click chemistry is used to reprogram natural flavonoids into covalent inhibitors with enhanced α‐glucosidase selectivity and controlled reactivity. This strategy enables effective regulation of carbohydrate digestion
Fengyu Guo, Liwei Zhang, Minlong Wang, Yanjin Du, Tianyu Zhang, Hao Chen, Jiazeng Sun, Yang Yu, Zude He, Jie An, Xiaoxu Zhang, Weilin Lin, Fazheng Ren, Pengjie Wang, Ping Liu   +14 more
wiley   +1 more source

Role of A-Kinase Anchoring Protein 12 in the Central Nervous System. [PDF]

J Clin Neurol, 2023
Kimura S, Lok J, Gelman IH, Lo EH, Arai K.   +4 more
europepmc   +1 more source

PRMT9 Aggravated Dopaminergic Neurodegeneration in Parkinson's Disease Model by Facilitating the Degradation of DUSP26 and Inducing Mitochondrial Dysfunction

Advanced Science, EarlyView.
In the pathological state of PD induced by MPP+, the upregulated PRMT9 in dopaminergic neurons translocates into mitochondrion and interacts with DUSP26 and catalyzes its arginine methylation, leading to the ubiquitin‐proteasomal degradation of DUSP26 mediated by Trim32.
Tengfei Liu, Xiaomeng Song, Xin Guo, Rui Xiao, Ru Sun, Qiuran Ji, Lu Yu, Yiquan Li, Qingyi Fu, Qidi Xue, Lingjun Kong, Lin Chen, Chengjiang Gao, Huiqing Liu   +13 more
wiley   +1 more source

Subcellular drug targeting illuminates local kinase action

eLife, 2019
Deciphering how signaling enzymes operate within discrete microenvironments is fundamental to understanding biological processes. A-kinase anchoring proteins (AKAPs) restrict the range of action of protein kinases within intracellular compartments.
Paula J Bucko, Chloe K Lombard, Lindsay Rathbun, Irvin Garcia, Akansha Bhat, Linda Wordeman, F Donelson Smith, Dustin J Maly, Heidi Hehnly, John D Scott   +9 more
doaj   +1 more source

Endobody: Genetically Encodable Nanobody‐CPP Chimeras for Degradation of Membrane and Extracellular Proteins

Advanced Science, EarlyView.
We introduced genetically encodable, receptor‐independent nanobody‐CPP chimeras, termed endobodies, as robust and modular membrane protein degraders. Additionally, proteasome‐targeting domain (PTD)‐tethered endobody demonstrates further enhanced degradation potency.
Chengjian Zhou, Huiping He, Simin Xia, Xi Chen   +3 more
wiley   +1 more source