Repurposing simeprevir uncovers a druggable KPNB1-p65-BCL2 survival axis in cancer [0.03%]
再利用simeprevir发现癌症中可药用的KPNB1-p65-BCL2生存轴
Cong Li,Qiaohua Yan,Muhammad Muddasar Saeed et al.
Cong Li et al.
Proper subcellular protein localization is fundamental for protein function, yet cancer cells often exploit this machinery for survival. While the nuclear import receptor KPNB1 (importin β1) is overexpressed in various cancers, its oncogen...
Tae Ha Kim,Chi Thi Ngoc Nguyen,Dahee Jang et al.
Tae Ha Kim et al.
Coenzyme Q (CoQ) is an essential electron carrier and lipophilic antioxidant whose biological functions depend on its redox state. However, accurate measurement of reduced and oxidized CoQ is hindered by rapid ex vivo oxidation during sampl...
Logan Elkin,Evgeny G Chulkov,Jonathan D Enders et al.
Logan Elkin et al.
Benzodiazepines are widely prescribed therapeutics whose actions are primarily attributed to the modulation of GABAA receptors. Here, we identify a previously unrecognized target of a subset of benzodiazepines-the cold- and menthol-sensitiv...
A protective human antibody reveals a quaternary epitope on the Epstein-Barr virus fusion apparatus [0.03%]
一种具有保护作用的人类抗体揭示了爱泼斯坦-巴尔病毒融合装置上的四级表位
Ge-Xin Zhao,Xin-Yan Fang,Ting Li et al.
Ge-Xin Zhao et al.
Epstein-Barr virus (EBV) entry into B lymphocytes and epithelial cells requires the conserved fusion machinery gHgL and the tropism-switching glycoprotein gp42. While the individual roles of these proteins have been extensively studied, the...
Multinuclear iron enzymes expand RiPP chemical diversity to enable bacterial oxidative stress defense [0.03%]
多核铁酶使RiPP化学多样性多样化以增强细菌的氧化应激防御能力
Hanzhong Feng,Hang Xu,Zhuangzhuang Chu et al.
Hanzhong Feng et al.
RiPP structural complexity is significantly expanded by multinuclear non-heme iron-dependent oxidative enzymes (MNIOs). Here, we characterize pseudoprobactin 1 and 2, two MNIO-modified proteins from Pseudomonas protegens Pf-5. Using MS, NMR...
N-acetyltransferase 10 regulates chemokine expression in keratinocytes and promotes atopic dermatitis [0.03%]
角蛋白酶N-乙酰转移酶10调节作用于棘层细胞的化学趋化因子表达并促进特应性皮炎的发展
Jinjin Shao,Linying Wang,Zhichao Ye et al.
Jinjin Shao et al.
Atopic dermatitis (AD) is a chronic relapsing inflammatory skin disorder with complex immunological underpinnings, yet the role of the RNA acetyltransferase NAT10 in its pathogenesis remains unclear. We investigated NAT10 function through c...
Dual-function PROTAC suppresses ferroptosis and restores neuronal function via brain-targeted delivery [0.03%]
双功能PROTAC抑制铁死亡并恢复神经元功能的脑靶向递送研究
Tianyu Ma,Tianli Luo,Ming Wang
Tianyu Ma
Targeted protein degradation (TPD) via proteolysis-targeting chimeras (PROTACs) offers a promising strategy for modulating disease-associated proteins, yet effective brain-preferred protein degradation remains challenging. Herein, we report...
Aptamer targeting HMGB1 attenuates inflammatory disease via domain-specific antagonism [0.03%]
特异性结合HMGB1的核酸适配体通过特异抑制作用缓解炎症疾病
Hui Zhang,Lele Ma,Shaoju Gan et al.
Hui Zhang et al.
Damage-associated molecular patterns (DAMPs) are key mediators of inflammatory disease, among which HMGB1 is a prototypical extracellular alarmin and an attractive therapeutic target. Here, we report ZH-1a, a high-affinity DNA aptamer (Kd =...
The pyruvate dehydrogenase complex at the crossroads of cancer metabolism and cell death [0.03%]
处于癌症代谢和细胞死亡交叉路口的丙酮酸脱氢酶复合体
Xiutao Cai,Fangquan Chen,Ruirui Liang et al.
Xiutao Cai et al.
The pyruvate dehydrogenase complex (PDHC) is a key metabolic hub that couples glycolysis-derived carbon flux to the tricarboxylic acid cycle and mitochondrial function. Its activity is regulated by pyruvate dehydrogenase kinases, phosphatas...
BACH1 meets its match: Heme licenses BACH1 destruction to tune ferroptosis [0.03%]
BACH1遇上对手：血红素通过诱导BACH1降解调节铁死亡
Dylan Calhoon,Javier Garcia-Bermudez
Dylan Calhoon
In a recent issue of Molecular Cell, Ahmed and colleagues1 show that heme enables CRL2-FEM1B to recognize and degrade BACH1, linking metabolite-assisted substrate recruitment to ferroptosis regulation. This mechanism connects heme sensing, ...