CDK2 heterobifunctional degraders co-degrade CDK2 and cyclin E resulting in efficacy in CCNE1-amplified and overexpressed cancers [0.03%]
异二功能型CDK2降解剂可同时降解CDK2和cyclin E，在CCNE1拷贝数增加或过表达的癌症中表现出良好的疗效
Nicholas Kwiatkowski,Tong Liang,Zhe Sha et al.
Nicholas Kwiatkowski et al.
CCNE1 amplification drives aberrant CDK2-cyclin E1 activity in cancer. Despite activity of CDK2 inhibitors, their therapeutic margins are limited by poor CDK selectivity. We developed a degrader with high selectivity for CDK2 over CDK1 that...
Molecular mechanism of PP2A/B55α phosphatase inhibition by IER5 [0.03%]
IER5通过结合并抑制B55α亚基来抑制PP2A酶的分子机制研究
Ruili Cao,Daniel T D Jones,Li Pan et al.
Ruili Cao et al.
PP2A serine/threonine phosphatases are heterotrimeric complexes that execute many essential physiologic functions. These activities are modulated by additional regulatory proteins, such as ARPP19, FAM122A, and IER5. Here, we report the cryo...
Streptomycin targets tumor-initiating cells by disrupting oxidative phosphorylation [0.03%]
链霉素通过干扰氧化磷酸化作用靶向肿瘤起始细胞
Hélène Guillorit,Sébastien Relier,Benjamin Zagiel et al.
Hélène Guillorit et al.
Tumor initiating cells (TICs) are the roots of current shortcomings in advanced and metastatic cancer treatment. Endowed with self-renewal and multi-lineage differentiation capacity, TICs can disseminate and seed metastasis in distant organ...
Natural products chlorotonils exert a complex antibacterial mechanism and address multiple targets [0.03%]
天然产物氯化茋类化合物具有复杂的抗菌机制并针对多个靶点发挥作用
Felix Deschner,Dietrich Mostert,Jan-Martin Daniel et al.
Felix Deschner et al.
Antimicrobial resistance is a threat to human health rendering current first-line antibiotics ineffective. New agents overcoming resistance mechanisms are urgently needed to guarantee successful treatment of human disease in the future. Chl...
Understanding, inhibiting, and engineering membrane transporters with high-throughput mutational screens [0.03%]
高通量突变筛选在膜转运蛋白的理解、抑制及工程化中的应用
Silas T Miller,Christian B Macdonald,Srivatsan Raman
Silas T Miller
Promiscuous membrane transporters play vital roles across domains of life, mediating the uptake and efflux of structurally and chemically diverse substrates. Although many transporter structures have been solved, the fundamental rules of po...
Visualization of calpain-1 activation during cell death and its role in GSDMD cleavage using chemical probes [0.03%]
利用化学探针可视化细胞死亡过程中钙蛋白酶-1的激活及其在GSDMD裂解中的作用
Natalia Horbach,Małgorzata Kalinka,Natalia Ćwilichowska-Puślecka et al.
Natalia Horbach et al.
Calpain-1, a calcium-dependent cysteine protease, plays a vital role in cellular processes such as cell death, cytoskeletal remodeling, signal transduction, and cell cycle progression. While its role in apoptosis, including substrate cleava...
Targeted degradation of CDK9 potently disrupts the MYC-regulated network [0.03%]
CDK9的靶向降解有力地破坏了MYC调节网络
Mohammed A Toure,Keisuke Motoyama,Yichen Xiang et al.
Mohammed A Toure et al.
CDK9 coordinates signaling events that regulate transcription and is implicated in oncogenic pathways, making it an actionable target for drug development. While numerous CDK9 inhibitors have been developed, success in the clinic has been l...
Epigenetic fluidity meets phenotypic malleability in intestinal epithelial cells [0.03%]
肠上皮细胞中的表观遗传流动性遇上了表现型可塑性
Swarnabh Bhattacharya,Ramesh A Shivdasani
Swarnabh Bhattacharya
Differentiated progenitors in intestinal crypts react to stem cell attrition by reverting to the multipotent state. In the February issue of Nature Cell Biology, Pashos et al.1 reveal a role for H3K36 methylation at cell-type-restricted gen...
Cheng-En Shen,Alesandra S Echeandía Marrero,Yuan Pan
Cheng-En Shen
Neurons are key to brain tumor pathogenesis. Though direct synaptic connections between neurons and glioblastoma cells had been revealed, the nature of such connections remained enigmatic. In a recent issue of Cell, Tetzlaff et al.1 leverag...
Madison S Mortensen,Jennifer L Watts
Madison S Mortensen
Polyunsaturated fats promote ferroptosis through their propensity to form toxic lipid peroxides. In this issue of Cell Chemical Biology, Sokol et al.1 report that extracellular lipid depletion leads to increased cell death by ferroptosis. T...