Proteomics of broad deubiquitylase inhibition unmasks redundant enzyme function to reveal substrates and assess enzyme specificity [0.03%]
泛去泛素化酶抑制的蛋白质组学揭露出冗余酶功能以揭示底物和评估酶特异性
Valentina Rossio,Joao A Paulo,Joel Chick et al.
Valentina Rossio et al.
Deubiquitylating enzymes (DUBs) counteract ubiquitylation to control stability or activity of substrates. Identification of DUB substrates is challenging because multiple DUBs can act on the same substrate, thwarting genetic approaches. Her...
Functional mimicry revealed by the crystal structure of an eIF4A:RNA complex bound to the interfacial inhibitor, desmethyl pateamine A [0.03%]
desmethyl Pateamine A 结合的 eIF4A:RNA 复合物晶体结构揭示了功能模拟现象
Sai Kiran Naineni,Jason Liang,Kenneth Hull et al.
Sai Kiran Naineni et al.
Interfacial inhibitors exert their biological effects through co-association with two macromolecules. The pateamine A (PatA) class of molecules function by stabilizing eukaryotic initiation factor (eIF) 4A RNA helicase onto RNA, resulting i...
Targeted degradation of the enhancer lysine acetyltransferases CBP and p300 [0.03%]
靶向降解CBP和p300增强子乙酰转移酶
Raghu Vannam,Jan Sayilgan,Samuel Ojeda et al.
Raghu Vannam et al.
The enhancer factors CREB-binding protein (CBP) and p300 (also known as KAT3A and KAT3B) maintain gene expression programs through lysine acetylation of chromatin and transcriptional regulators and by scaffolding functions mediated by sever...
Resident and elicited murine macrophages differ in expression of their glycomes and glycan-binding proteins [0.03%]
小鼠驻留巨噬细胞和感应巨噬细胞的糖类蛋白质组及其糖结合蛋白表达不同
Diane D Park,Jiaxuan Chen,Matthew R Kudelka et al.
Diane D Park et al.
The pleiotropic functions of macrophages in immune defense, tissue repair, and maintenance of tissue homeostasis are supported by the heterogeneity in macrophage sub-populations that differ both in ontogeny and polarization. Although glycan...
Jaeyoung Ha,Hankum Park,Jongmin Park et al.
Jaeyoung Ha et al.
Phenotype-based screening has emerged as an alternative route for discovering new chemical entities toward first-in-class therapeutics. However, clarifying their mode of action has been a significant bottleneck for drug discovery. For targe...
Discovery of cellular substrates of human RNA-decapping enzyme DCP2 using a stapled bicyclic peptide inhibitor [0.03%]
人RNA脱帽酶DCP2的细胞底物的发现使用了夹闭双环肽抑制剂
Yang Luo,Jeremy A Schofield,Zhenkun Na et al.
Yang Luo et al.
DCP2 is an RNA-decapping enzyme that controls the stability of human RNAs that encode factors functioning in transcription and the immune response. While >1,800 human DCP2 substrates have been identified, compensatory expression changes sec...
Lipid-derived electrophiles mediate the effects of chemotherapeutic topoisomerase I poisons [0.03%]
由脂质衍生的亲介导化疗拓扑异构酶I毒物的作用
Amy Flor,Donald Wolfgeher,Jing Li et al.
Amy Flor et al.
Topoisomerase 1 (Top1) reversibly nicks chromosomal DNA to relax strain accumulated during transcription, replication, chromatin assembly, and chromosome condensation. The Top1 poison camptothecin targets cancer cells by trapping the enzyme...
Mariano A Garcia-Blanco
Mariano A Garcia-Blanco
In this issue of Cell Chemical Biology, Shibata et al. (2020) rescue expression of CFTR from a defective gene by inhibiting splicing factors required for the inclusion of a pathogenic pseudo exon. Their work highlights the untapped potentia...
An IMiD-inducible degron provides reversible regulation for chimeric antigen receptor expression and activity [0.03%]
一种IMiD诱导的降解域可实现嵌合抗原受体表达和活性的可逆调节
Seth Carbonneau,Sujata Sharma,Liaomin Peng et al.
Seth Carbonneau et al.
The recent development of successful CAR (chimeric antigen receptor) T cell therapies has been accompanied by a need to better control potentially fatal toxicities that can arise from adverse immune reactions. Here we present a ligand-contr...
Hypomorph mutation-directed small-molecule protein-protein interaction inducers to restore mutant SMAD4-suppressed TGF-β signaling [0.03%]
低渗突变体导向的小分子蛋白质相互作用诱导剂可恢复SMAD4变异体所抑制的TGF-β信号转导路径
Cong Tang,Xiulei Mo,Qiankun Niu et al.
Cong Tang et al.
Tumor suppressor genes represent a major class of oncogenic drivers. However, direct targeting of loss-of-function tumor suppressors remains challenging. To address this gap, we explored a variant-directed chemical biology approach to rever...