Plasmodium falciparum HSP90 inhibitors show divergent resistance despite a shared ATP-binding site [0.03%]
尽管存在相同的ATP结合位点 原疟凶毒热休克蛋白90抑制剂产生不同的耐药性
Fu-Hsuan Ko,Amanda K Lukens,Mariana Laureano de Souza et al.
Fu-Hsuan Ko et al.
Drug resistance poses a major challenge across therapeutic areas including malaria, yet factors governing resistance propensity remain poorly understood. We demonstrate that two HSP90 inhibitors targeting the identical ATP-binding site exhi...
Structural proteomics reveals that misfolded nascent proteins expose buried lysines for ubiquitination and rapid proteasomal degradation [0.03%]
结构蛋白组学揭示了错误折叠的新生蛋白质暴露赖氨酸用于泛素化和快速被蛋白酶体降解
Anushka Jain,Naiyareen F Mayeen,Michael E Meadow et al.
Anushka Jain et al.
The proteasome maintains the integrity of eukaryotic proteomes by selectively degrading ubiquitinated protein substrates. Ubiquitination targets a wide range of substrates for degradation, including translationally stalled nascent chains, m...
Physical interactions within the SIR heterochromatin complex potentiate inter-subunit communication and gene repression [0.03%]
SIR异染色质复合体内的物理相互作用可以增强亚基间的通讯并抑制基因表达
Jenna Kotz,E J Martz,Maya Nelson et al.
Jenna Kotz et al.
The Saccharomyces cerevisiae silent information regulator (SIR) complex performs all core heterochromatin functions. It first drives histone deacetylation in an iterative, spreading manner, then stably incorporates with nucleosomes to compa...
An IGF2BP3-dependent metabolic circuit governs macrophage recruitment and immunosuppression in glioblastoma [0.03%]
IGF2BP3依赖的代谢调控轴调控胶质母细胞瘤中的巨噬细胞浸润和免疫抑制作用
Weiwei Dai,Ruotong Tian,Ming Whye Chong et al.
Weiwei Dai et al.
The glioblastoma microenvironment is highly immunosuppressive and enriched with macrophages, which critically promote tumor progression and confer resistance to current therapies. However, the molecular mechanisms by which glioblastoma cell...
A cold-induced GDF15-secreting adipocyte subpopulation regulates energy homeostasis through endocrine signaling [0.03%]
冷诱导的GDF15分泌型脂肪细胞亚群通过内分泌信号调节能量平衡
Chunyan Wu,Tongtong Wang,Songlin Gong et al.
Chunyan Wu et al.
Brown adipose tissue (BAT) regulates whole-body energy balance through uncoupling protein 1 (UCP1)-dependent thermogenesis and secretion of metabolic factors. Recent studies suggest UCP1-independent mechanisms contribute to energy balance, ...
RelB drives integrin-mediated stress tolerance and relapse in high-grade serous ovarian cancer [0.03%]
RelB通过整合素介导的应力耐受和复发促进高级别浆液性卵巢癌发展
Omar Lujano-Olazaba,Mikella Robinson,Gregory J Jordan et al.
Omar Lujano-Olazaba et al.
High-grade serous ovarian cancer (HGSOC) often relapses after chemotherapy due to chemoresistant cancer stem-like cells (CSCs). NF-κB signaling, previously shown to enhance stemness traits, was investigated for its role in post-treatment t...
Yeast β-glucan supplementation supports immunometabolic anti-tumor responses and reverses obesity-induced dysfunction via trained hematopoiesis [0.03%]
酵母β-葡聚糖补充支持训练造血诱导的免疫代谢抗肿瘤反应并逆转肥胖引起的造血功能障碍
Anna E Ledwith,Hannah Prendeville,Cian Jh Horneck Johnston et al.
Anna E Ledwith et al.
Obesity is associated with profound immune dysregulation, driving chronic inflammation while compromising host defense against tumors. While trained immunity can enhance innate effector functions, it has thus far required parenteral adminis...
Structural and evolutionary divergence of the RAG1/1L N-terminal zinc-coordinating domain [0.03%]
RAG1/1L N末端锌配位结构域的结构和进化差异
Junye Hong,Zhijun Liu,Wei Xu et al.
Junye Hong et al.
RAG1/2 catalyzes V(D)J recombination to assemble antigen receptor genes, but the RAG1 N-terminal zinc-coordinating domain (NZD) has remained structurally and functionally uncharacterized. Here, we determine the NMR structure of mouse RAG1 N...
BCAA metabolism promotes lung cancer tumorigenesis by enhancing cholesterol biosynthesis [0.03%]
亮氨酸代谢通过促进胆固醇生物合成驱动肺癌发生发展
Huimin Ma,Erbao Zhang,Jiaying Cai et al.
Huimin Ma et al.
Metabolic dysregulation has been established as a key driver in tumorigenesis, but its underlying mechanisms in lung cancer remain poorly characterized. In this study, we performed nested case-control analyses in two prospective cohorts (20...
Yap mediates hippo signaling to balance proliferation and differentiation in the developing glandular stomach epithelium [0.03%]
Yap通过介导Hippo信号传导来调节发育中胃上皮细胞增殖和分化之间的平衡
Rongzi Mu,Jiangying Liu,Dan Luo et al.
Rongzi Mu et al.
The glandular stomach is an important digestive organ, and its proper epithelial development is essential for its normal structure and function. However, the molecular mechanisms underlying its epithelial development remain largely unclear....