Regulation of the endocytosis and prion-chaperoning machineries by yeast E3 ubiquitin ligase Rsp5 as revealed by orthogonal ubiquitin transfer [0.03%]
正交泛素转移揭示酿酒酵母E3泛素连接酶Rsp5调控内吞途径和朊病毒辅助元的功能
Yiyang Wang,Shuai Fang,Geng Chen et al.
Yiyang Wang et al.
Attachment of the ubiquitin (UB) peptide to proteins via the E1-E2-E3 enzymatic machinery regulates diverse biological pathways, yet identification of the substrates of E3 UB ligases remains a challenge. We overcame this challenge by constr...
A small-molecule inhibitor of the BRCA2-RAD51 interaction modulates RAD51 assembly and potentiates DNA damage-induced cell death [0.03%]
一种BRCA2-RAD51互作的小分子抑制剂可调节RAD51装配并促进DNA损伤诱导的细胞死亡
Duncan E Scott,Nicola J Francis-Newton,May E Marsh et al.
Duncan E Scott et al.
BRCA2 controls RAD51 recombinase during homologous DNA recombination (HDR) through eight evolutionarily conserved BRC repeats, which individually engage RAD51 via the motif Phe-x-x-Ala. Using structure-guided molecular design, templated on ...
Chiho Kim,Chuo Chen,Yonghao Yu
Chiho Kim
PARP1 is a poly(ADP-ribose) polymerase (PARP) enzyme that plays a critical role in regulating DNA damage response. The main enzymatic function of PARP1 is to catalyze a protein post-translational modification known as poly(ADP-ribosyl)ation...
J Jeya Vandana,Lauretta A Lacko,Shuibing Chen
J Jeya Vandana
The high-throughput phenotypic screen (HTPS) has become an emerging technology to discover synthetic small molecules that regulate stem cell fates. Here, we review the application of HTPS to identify small molecules controlling stem cell re...
Modulation of lanosterol synthase drives 24,25-epoxysterol synthesis and oligodendrocyte formation [0.03%]
兰斯特醇合酶的调控驱动24,25-环氧甾醇合成及少突胶质细胞形成
Zita Hubler,Ryan M Friedrich,Joel L Sax et al.
Zita Hubler et al.
Small molecules that promote the formation of new myelinating oligodendrocytes from oligodendrocyte progenitor cells (OPCs) are potential therapeutics for demyelinating diseases. We recently established inhibition of specific cholesterol bi...
Re-defining synthetic lethality by phenotypic profiling for precision oncology [0.03%]
通过表型分析重新定义合成致死作用以实现精准肿瘤学
Yevhen Akimov,Tero Aittokallio
Yevhen Akimov
High-throughput functional and genomic screening techniques provide systematic means for phenotypic discovery. Using synthetic lethality (SL) as a paradigm for anticancer drug and target discovery, we describe how these screening technologi...
Gene editing and synthetically accessible inhibitors reveal role for TPC2 in HCC cell proliferation and tumor growth [0.03%]
基因编辑和合成可获得的抑制剂揭示TPC2在肝癌细胞增殖和肿瘤生长中的作用
Martin Müller,Susanne Gerndt,Yu-Kai Chao et al.
Martin Müller et al.
The role of two-pore channel 2 (TPC2), one of the few cation channels localized on endolysosomal membranes, in cancer remains poorly understood. Here, we report that TPC2 knockout reduces proliferation of cancer cells in vitro, affects thei...
Quantitative chemoproteomics reveals O-GlcNAcylation of cystathionine γ-lyase (CSE) represses trophoblast syncytialization [0.03%]
定量化学蛋白质组学揭示O-GlcNAc修饰的半胱氨酸γ-裂解酶(CSE)抑制滋养细胞合体化
Juan Liu,Xuan Shao,Wei Qin et al.
Juan Liu et al.
Emerging evidence indicates the involvement of O-GlcNAc modification in placental development and pregnant health through mechanisms that are not well understood. Herein, by applying the quantitative O-GlcNAc proteomics, we established a da...
A synthetic diterpene analogue inhibits mycobacterial persistence and biofilm formation by targeting (p)ppGpp synthetases [0.03%]
一种合成倍半萜衍生物通过靶向(m)p ppGpp 合酶抑制分枝杆菌休眠和生物被膜的形成
Alexander G Tkachenko,Natalya M Kashevarova,Roman Yu Sidorov et al.
Alexander G Tkachenko et al.
Bacterial persistence coupled with biofilm formation is directly associated with failure of antibiotic treatment of tuberculosis. We have now identified 4-(4,7-DiMethyl-1,2,3,4-tetrahydroNaphthalene-1-yl)Pentanoic acid (DMNP), a synthetic d...
Efficient inhibition of O-glycan biosynthesis using the hexosamine analog Ac5GalNTGc [0.03%]
高效抑制O-聚糖生物合成的己糖胺类似物Ac5GalNTGc
Shuen-Shiuan Wang,Virginia Del Solar,Xinheng Yu et al.
Shuen-Shiuan Wang et al.
There is a critical need to develop small-molecule inhibitors of mucin-type O-linked glycosylation. The best-known reagent currently is benzyl-GalNAc, but it is effective only at millimolar concentrations. This article demonstrates that Ac5...