Distinct Mechanisms of Resistance to a CENP-E Inhibitor Emerge in Near-Haploid and Diploid Cancer Cells [0.03%]
近二倍体和二倍体癌细胞中针对有丝分裂检查点激酶CENP-E的抑制剂产生不同的耐药机制
Rudolf Pisa,Donovan Y Z Phua,Tarun M Kapoor
Rudolf Pisa
Aberrant chromosome numbers in cancer cells may impose distinct constraints on the emergence of drug resistance-a major factor limiting the long-term efficacy of molecularly targeted therapeutics. However, for most anticancer drugs we lack ...
Evan M Kerek,Christopher R Cromwell,Basil P Hubbard
Evan M Kerek
In this issue of Cell Chemical Biology, Erdogan et al. (2020) describe a new CRISPR/Cas9-based strategy for performing directed evolution of mammalian proteins in situ. Using this technique to select functional mRuby3 variants within lysoso...
Simon Hansen,Rami N Hannoush
Simon Hansen
In this issue of Cell Chemical Biology, Chen et al. (2020) present an antibody-based platform to generate Wnt agonists, offering multiple design principles for systematic investigation of Wnt activation. This study lays the groundwork to de...
Regulation of MIF Enzymatic Activity by an Allosteric Site at the Central Solvent Channel [0.03%]
调节MIF酶活性的别构位点位于中央溶剂通道中
Georgios Pantouris,Leepakshi Khurana,Anthony Ma et al.
Georgios Pantouris et al.
In proteins with multiple functions, such as macrophage migration inhibitory factor (MIF), the study of its intramolecular dynamic network can offer a unique opportunity to understand how a single protein is able to carry out several nonove...
Targeting Two-Component Systems Uncovers a Small-Molecule Inhibitor of Salmonella Virulence [0.03%]
针对双组分系统筛选靶标发现了一个沙门氏菌毒力抑制剂小分子
Caressa N Tsai,Craig R MacNair,My P T Cao et al.
Caressa N Tsai et al.
Salmonella serovars are leading causes of gastrointestinal disease and have become increasingly resistant to fluoroquinolone and cephalosporin antibiotics. Overcoming this healthcare crisis requires new approaches in antibiotic discovery an...
A Cell-Based Target Engagement Assay for the Identification of Cereblon E3 Ubiquitin Ligase Ligands and Their Application in HDAC6 Degraders [0.03%]
基于细胞的靶点 engagement 实验在识别 CRBN E3 ubiquitin ligase 底物及去卷积 HDAC6 分子胶中的应用
Ka Yang,Yu Zhao,Xueqing Nie et al.
Ka Yang et al.
Proteolysis-targeting chimeras (PROTACs) is a paradigm shift for small-molecule drug discovery. However, limited E3 ubiquitin ligase ligands with cellular activity are available. In vitro binding assays involve the expression and purificati...
Identification of a Covalent Molecular Inhibitor of Anti-apoptotic BFL-1 by Disulfide Tethering [0.03%]
基于二硫键连接体鉴定抗凋亡蛋白BFL-1的共价小分子抑制剂
Edward P Harvey,Zachary J Hauseman,Daniel T Cohen et al.
Edward P Harvey et al.
The BCL-2 family is composed of anti- and pro-apoptotic members that respectively protect or disrupt mitochondrial integrity. Anti-apoptotic overexpression can promote oncogenesis by trapping the BCL-2 homology 3 (BH3) "killer domains" of p...
Louvy Lynn Punzalan,Lulu Jiang,Di Mao et al.
Louvy Lynn Punzalan et al.
Pharmacophore-focused chemical libraries are continuously being created in drug discovery programs, yet screening assays to maximize the usage of such libraries are not fully explored. Here, we report a chemical proteomics approach to reuti...
A Plasma Protein Network Regulates PM20D1 and N-Acyl Amino Acid Bioactivity [0.03%]
一种血浆蛋白质网络调节PM20D1和N-酰基氨基酸的活性
Joon T Kim,Mark P Jedrychowski,Wei Wei et al.
Joon T Kim et al.
N-acyl amino acids are a family of cold-inducible circulating lipids that stimulate thermogenesis. Their biosynthesis is mediated by a secreted enzyme called PM20D1. The extracellular mechanisms that regulate PM20D1 or N-acyl amino acid act...
Targeted Degradation of SLC Transporters Reveals Amenability of Multi-Pass Transmembrane Proteins to Ligand-Induced Proteolysis [0.03%]
SLC转运蛋白的靶向降解揭示了多跨膜蛋白可诱导蛋白水解的敏感性
Ariel Bensimon,Mattia D Pizzagalli,Felix Kartnig et al.
Ariel Bensimon et al.
With more than 450 members, the solute carrier (SLC) group of proteins represents the largest class of transporters encoded in the human genome. Their several-pass transmembrane domain structure and hydrophobicity contribute to the orphan s...