Sulfotyrosine-Mediated Recognition of Human Thrombin by a Tsetse Fly Anticoagulant Mimics Physiological Substrates [0.03%]
通过硫酸酪氨酸,采采蝇抗凝剂对人凝血酶的识别类似于生理底物的过程
Bárbara M Calisto,Jorge Ripoll-Rozada,Luke J Dowman et al.
Bárbara M Calisto et al.
Despite possessing only 32 residues, the tsetse thrombin inhibitor (TTI) is among the most potent anticoagulants described, with sub-picomolar inhibitory activity against thrombin. Unexpectedly, TTI isolated from the fly is 2000-fold more a...
Dipyridamole Inhibits Lipogenic Gene Expression by Retaining SCAP-SREBP in the Endoplasmic Reticulum [0.03%]
双嘧达莫通过使SCAP-SREBP保留在内质网来抑制脂生成基因的表达
Ryan M Esquejo,Manuel Roqueta-Rivera,Wei Shao et al.
Ryan M Esquejo et al.
Sterol regulatory element-binding proteins (SREBPs) are master transcriptional regulators of the mevalonate pathway and lipid metabolism and represent an attractive therapeutic target for lipid metabolic disorders. SREBPs are maintained in ...
Modulating Androgen Receptor-Driven Transcription in Prostate Cancer with Selective CDK9 Inhibitors [0.03%]
用选择性CDK9抑制剂调节前列腺癌中雄激素受体驱动的转录
André Richters,Shelby K Doyle,David B Freeman et al.
André Richters et al.
Castration-resistant prostate cancers (CRPCs) lose sensitivity to androgen-deprivation therapies but frequently remain dependent on oncogenic transcription driven by the androgen receptor (AR) and its splice variants. To discover modulators...
The Right Tool for the Job: A Chemical and Genetic Toolkit for Interrogating DCLK1 Function [0.03%]
适合的工作工具：用于探究DCLK1功能的化学和基因工具箱
Linglan Fang,Dustin J Maly
Linglan Fang
Cell permeable, small molecule inhibitors are powerful tools for interrogating kinase function and validating drug targets. In this issue of Cell Chemical Biology, Liu and colleagues (2020) describe the development of a toolkit containing a...
Discovery of an Unnatural DNA Modification Derived from a Natural Secondary Metabolite [0.03%]
来自天然次级代谢产物的非自然DNA修饰物的发现
Tong Wang,Rahul M Kohli
Tong Wang
Despite widespread interest for understanding how modified bases have evolved their contemporary functions, limited experimental evidence exists for measuring how close an organism is to accidentally creating a new, modified base within the...
Proteomics-Based Identification of DUB Substrates Using Selective Inhibitors [0.03%]
基于蛋白质组学的DUB底物鉴定使用选择性抑制剂方法
Jonathan W Bushman,Katherine A Donovan,Nathan J Schauer et al.
Jonathan W Bushman et al.
Deubiquitinating enzymes (DUBs) catalyze the removal of ubiquitin, thereby reversing the activity of E3 ubiquitin ligases and are central to the control of protein abundance and function. Despite the growing interest in DUBs as therapeutic ...
A Method for Conditional Regulation of Protein Stability in Native or Near-Native Form [0.03%]
一种用于调节蛋白质在天然或接近天然状态下稳定性的方法
Yusaku Miyamae,Ling-Chun Chen,Yuki Utsugi et al.
Yusaku Miyamae et al.
Here, we report a method to regulate cellular protein levels by introducing a ubiquitin variant between a destabilizing domain (DD) and the regulated protein. When produced in the absence of a stabilizing ligand the DD dominates and the ent...
Quantitative Imaging of Labile Zn2+ in the Golgi Apparatus Using a Localizable Small-Molecule Fluorescent Probe [0.03%]
利用可定位的小分子荧光探针定量成像高尔基体中的不稳定锌离子
Toshiyuki Kowada,Tomomi Watanabe,Yuta Amagai et al.
Toshiyuki Kowada et al.
Fluorescent Zn2+ probes used for the quantitative analysis of labile Zn2+ concentration ([Zn2+]) in target organelles are crucial for understanding the role of Zn2+ in biological processes. Although several fluorescent Zn2+ probes have been...
Photoaffinity Labeling and Quantitative Chemical Proteomics Identify LXRβ as the Functional Target of Enhancers of Astrocytic apoE [0.03%]
光亲和标记和定量化学生物学鉴定LXRβ为星形胶质细胞apoE增强子的功能靶点
Uthpala Seneviratne,Zhen Huang,Christopher W Am Ende et al.
Uthpala Seneviratne et al.
Utilizing a phenotypic screen, we identified chemical matter that increased astrocytic apoE secretion in vitro. We designed a clickable photoaffinity probe based on a pyrrolidine lead compound and carried out probe-based quantitative chemic...
Identification of Small-Molecule Activators of the Ubiquitin Ligase E6AP/UBE3A and Angelman Syndrome-Derived E6AP/UBE3A Variants [0.03%]
小分子激活剂对泛素连接酶E6AP / UBE3A和源自天使人综合征的E6AP / UBE3A变异体的鉴定
Fabian Offensperger,Franziska Müller,Jasmin Jansen et al.
Fabian Offensperger et al.
Genetic aberrations of the UBE3A gene encoding the E3 ubiquitin ligase E6AP underlie the development of Angelman syndrome (AS). Approximately 10% of AS individuals harbor UBE3A genes with point mutations, frequently resulting in the express...