Tracking the PROTAC degradation pathway in living cells highlights the importance of ternary complex measurement for PROTAC optimization [0.03%]
在活细胞中追踪PROTAC降解途径强调了定量三元复合物以优化PROTAC的重要性
Martin P Schwalm,Andreas Krämer,Anja Dölle et al.
Martin P Schwalm et al.
The multi-step degradation process of PROteolysis TArgeting Chimeras (PROTACs) poses a challenge for their rational development, as the rate-limiting steps that determine PROTACs efficiency remain largely unknown. Moreover, the slow through...
Peptide-mediated inhibition of the transcriptional regulator Elongin BC induces apoptosis in cancer cells [0.03%]
肽介导的转录调节剂Elongin BC抑制可诱导癌细胞凋亡
Sabrina Fischer,Van Tuan Trinh,Clara Simon et al.
Sabrina Fischer et al.
Inhibition of protein-protein interactions (PPIs) via designed peptides is an effective strategy to perturb their biological functions. The Elongin BC heterodimer (ELOB/C) binds to a BC-box motif and is essential for cancer cell growth. Her...
TRIM21 is a druggable target for the treatment of metastatic colorectal cancer through ubiquitination and activation of MST2 [0.03%]
TRIM21是通过泛素化和激活MST2治疗转移性结直肠癌的药物靶点
Yu-Xuan Liu,Shan Wan,Xiao-Qin Yang et al.
Yu-Xuan Liu et al.
Metastatic colorectal cancer (mCRC) is characterized by poorer prognosis of patients and limited therapeutic approach, partly due to the lack of effective target. Using mouse models and tumor organoids, this study reported a tripartite moti...
Vitalii S Basistyi,James H Frederich
Vitalii S Basistyi
In this issue of Cell Chemical Biology, Andlovic et al.1 unravel how certain fusicoccin toxins synergize with interferon-α to kill cancer cells. The results suggest that fusicoccins potentiate apoptosis by "sticking together" 14-3-3 protei...
ROTACs leverage signaling-incompetent R-spondin for targeted protein degradation [0.03%]
利用信号传导无能的R-因子回应蛋白实现靶向蛋白质降解
Rui Sun,Zibo Meng,Hyeyoon Lee et al.
Rui Sun et al.
Proteolysis-targeting chimeras (PROTACs) are an emerging technology for therapeutic intervention, but options to target cell surface proteins and receptors remain limited. Here we introduce ROTACs, bispecific WNT- and BMP-signaling-disabled...
Light-triggered site-directed RNA editing by endogenous ADAR1 with photolabile guide RNA [0.03%]
利用光可裂解向导RNA触发内源性ADAR1的特定位点RNA编辑
Yu Zhang,Di Feng,Guanqun Mu et al.
Yu Zhang et al.
RNA A-to-I editing is a post-transcriptional modification pervasively occurring in cells. Artificial intervention of A-to-I editing at specific sites of RNA could also be achieved with guide RNA and exogenous ADAR enzymes. In contrast to pr...
New scaffolds for type II JAK2 inhibitors overcome the acquired G993A resistance mutation [0.03%]
新型非芳基型JAK2抑制剂可有效应对临床JAK2突变体G993A
Matthew L Arwood,Yao Liu,Shannon K Harkins et al.
Matthew L Arwood et al.
Recurrent JAK2 alterations are observed in myeloproliferative neoplasms, B-cell acute lymphoblastic leukemia, and other hematologic malignancies. Currently available type I JAK2 inhibitors have limited activity in these diseases. Preclinica...
Cancer cell-autonomous cGAS-STING response confers drug resistance [0.03%]
cGAS-STING信号通路通过诱导癌症干细胞特性介导肿瘤的耐药性
Qian-Ming Lv,Hui-Min Lei,Shi-Yi Wang et al.
Qian-Ming Lv et al.
The cGAS-STING pathway has long been recognized as playing a crucial role in immune surveillance and tumor suppression. Here, we show that when the pathway is activated in a cancer-cell-autonomous response manner, it confers drug resistance...
Sumirtha Balaratnam,Zachary R Torrey,David R Calabrese et al.
Sumirtha Balaratnam et al.
Neuroblastoma RAS (NRAS) is an oncogene that is deregulated and highly mutated in cancers including melanomas and acute myeloid leukemias. The 5' untranslated region (UTR) (5' UTR) of the NRAS mRNA contains a G-quadruplex (G4) that regulate...
General trends in the effects of VX-661 and VX-445 on the plasma membrane expression of clinical CFTR variants [0.03%]
VX-661和VX-445对囊性纤维化跨膜转导调节器临床突变型细胞膜表达影响的总体趋势分析
Andrew G McKee,Eli F McDonald,Wesley D Penn et al.
Andrew G McKee et al.
Cystic fibrosis (CF) is caused by mutations that compromise the expression and/or function of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Most people with CF harbor a common misfolded variant (ΔF508) th...