Chenwei Zhou,Sarah Wagner,Fu-Sen Liang
Chenwei Zhou
Epigenetic regulation plays a pivotal role in various biological and disease processes. Two key lines of investigation have been pursued that aim to unravel endogenous epigenetic events at particular genes (probing) and artificially manipul...
Molecular glues and bifunctional compounds: Therapeutic modalities based on induced proximity [0.03%]
分子胶和双功能化合物：基于诱导接近的治疗手段
Stuart L Schreiber
Stuart L Schreiber
This Perspective explores molecular glues and bifunctional compounds-proximity-inducing compounds-and offers a framework to understand and exploit their similarity to hotspots, missense mutations, and posttranslational modifications (PTMs)....
Mitochondrial RelA empowers mtDNA G-quadruplex formation for hypoxia adaptation in cancer cells [0.03%]
线粒体RelA通过促进癌细胞缺氧适应中的线粒体DNA G-四链体形成来增强肿瘤发展
Gui-Xue Tang,Mao-Lin Li,Cui Zhou et al.
Gui-Xue Tang et al.
Mitochondrial DNA (mtDNA) G-quadruplexes (G4s) have important regulatory roles in energy metabolism, yet their specific functions and underlying regulatory mechanisms have not been delineated. Using a chemical-genetic screening strategy, we...
Specificity profiling of deubiquitylases against endogenously generated ubiquitin-protein conjugates [0.03%]
脱泛素酶对内源泛素-蛋白连接物的特异性分析教授特定蛋白质脱泛素酶的能力对于理解其生物学功能至关重要。在这里，作者开发了一种高内涵方法来评估去泛素酶（DUB）在细胞提取物中对内源性底物的选择性，并使用这种方法绘制了人C19orf4蛋白（也称为UCHL5或KLHDC2a）的特征，这是一种新发现的UBL结合DUB。该分析确定了一系列与神经退行性疾病有关的蛋白质作为C19orf4样UBL结构域的相互作用伙伴和底物，并表明C19orf4优先去除K63连接的二泛素分子上的单个泛素亚基。
Valentina Rossio,Joao A Paulo,Xinyue Liu et al.
Valentina Rossio et al.
Deubiquitylating enzymes (DUBs) remove ubiquitin from proteins thereby regulating their stability or activity. Our understanding of DUB-substrate specificity is limited because DUBs are typically not compared to each other against many phys...
AspSnFR: A genetically encoded biosensor for real-time monitoring of aspartate in live cells [0.03%]
实时监测活细胞中天冬氨酸的遗传编码生物传感器AspSnFR
Lars Hellweg,Martin Pfeifer,Miroslaw Tarnawski et al.
Lars Hellweg et al.
Aspartate is crucial for nucleotide synthesis, ammonia detoxification, and maintaining redox balance via the malate-aspartate-shuttle (MAS). To disentangle these multiple roles of aspartate metabolism, tools are required that measure aspart...
Chemical interplay between gut microbiota and epigenetics: Implications in circadian biology [0.03%]
肠道微生物组与表观遗传学的化学相互作用在生物钟生物学中的影响
Samskrathi Aravinda Sharma,Sarah Olanrewaju Oladejo,Zheng Kuang
Samskrathi Aravinda Sharma
Circadian rhythms are intrinsic molecular mechanisms that synchronize biological functions with the day/night cycle. The mammalian gut is colonized by a myriad of microbes, collectively named the gut microbiota. The microbiota impacts host ...
Tools to investigate the cell surface: Proximity as a central concept in glycoRNA biology [0.03%]
研究细胞表面的工具——邻近性在糖链 RNA 生物学中的中心概念
Lauren Kageler,Jonathan Perr,Ryan A Flynn
Lauren Kageler
Proximity is a fundamental concept in chemistry and biology, referring to the convergence of molecules to facilitate new molecular interactions or reactions. Hybrid biopolymers like glycosylphosphatidylinositol (GPI)-anchored proteins, ubiq...
The septin modifier, forchlorfenuron, activates NLRP3 via a potassium-independent mitochondrial axis [0.03%]
Septin调节剂forchlorfenuron通过独立于钾的线粒体轴活化NLRP3
Caroline L Holley,Stefan Emming,Mercedes M Monteleone et al.
Caroline L Holley et al.
The Nod-like receptor protein 3 (NLRP3) inflammasome is activated by stimuli that induce perturbations in cell homeostasis, which commonly converge on cellular potassium efflux. NLRP3 has thus emerged as a sensor for ionic flux. Here, we id...
One-carbon unit supplementation fuels purine synthesis in tumor-infiltrating T cells and augments checkpoint blockade [0.03%]
一碳单位补充促进肿瘤浸润T细胞中的嘌呤合成并增强检查点封锁效应
Xincheng Xu,Zihong Chen,Caroline R Bartman et al.
Xincheng Xu et al.
Nucleotides perform important metabolic functions, carrying energy and feeding nucleic acid synthesis. Here, we use isotope tracing-mass spectrometry to quantitate contributions to purine nucleotides from salvage versus de novo synthesis. W...
Transient hydroxycholesterol treatment restrains TCR signaling to promote long-term immunity [0.03%]
瞬时羟基胆固醇处理可抑制TCR信号传导以促进长期免疫响应
Zhengxu Ren,Kun Wang,Yong Zhang et al.
Zhengxu Ren et al.
T cell receptor (TCR) plays a fundamental role in adaptive immunity, and TCR-T cell therapy holds great promise for treating solid tumors and other diseases. However, there is a noticeable absence of chemical tools tuning TCR activity. In o...