Results 151 to 160 of about 51,947 (207)

The Deubiquitinase UCHL1 Drives Susceptibility to Atrial Fibrillation by Stabilizing CaMKII‐δ

Advanced Science, EarlyView.
UCHL1 is highly upregulated in mice and patients with AF. UCHL1 directly binds to and removes K48‐linked polyubiquitin chains from CaMKII‐δ at K251 and enhances CaMKII‐δ stability, which activates RyR2, disrupts Ca2+ handling, and promotes AF. These findings establish UCHL1 as a critical regulator of CaMKII‐δ stability and AF‐related Ca2+ handling ...
Hai‐Lian Bi, Yu‐Hui Gu, Kai‐Wen Ren, Xiao‐Hong Yu, Yun‐Long Xia, Xiao‐Lei Yang, Hui‐Hua Li   +6 more
wiley   +1 more source

Persistent Zn2+ Influx‐Mediated Deacetylation of ANXA2 Regulates the “Zn2+‐Autophagic Flux” and Alleviates Intervertebral Disc Degeneration

Advanced Science, EarlyView.
Zinc transporter SLC39A14 sustains intracellular Zn2+ levels to activate SIRT3‑dependent ANXA2 deacetylation at K302. This modification weakens ANXA2‑mTOR binding and releases autophagic‑flux suppression in nucleus pulposus cells. Dysregulated Zn2+ homeostasis disrupts this axis to drive intervertebral disc degeneration.
Yuxin Jin, Yongcheng Chen, Yihao Xie, Dongyang Hu, Longhui Gong, Zhihua Chen, Linjie Chen, Minhao Gao, Qizhu Chen, Morgan Jones, Hui Wang, Xiuling You, Kenny Yat Hong Kwan, Shoutao Weng, Taidong Lyu, Xiang Chen, Yuxiao Zhu, Yusheng Wang, Bin Li, Xiangyang Wang, Xiaofeng Jia, Kailiang Zhou, Ouqiang Wu, Aimin Wu   +23 more
wiley   +1 more source

Epigenetic Silencing of CYYR1 Promotes Lung Adenocarcinoma Progression Through TRIM21‐Dependent Regulation of HMMR Stability

Advanced Science, EarlyView.
CYYR1 as an epigenetically dysregulated tumor‐suppressive factor that influences oncoprotein stability through TRIM21‐dependent HMMR regulation and reveals a potential therapeutic vulnerability in CYYR1‐deficient LUAD. The graphical illustration was created using FigDraw (www.figdraw.com).
Fengsheng Dai, Jingyi Tang, Huan Rong, Yu Wang, Xiangyi Zhou, Can Xu, Jianhua Wang, Lili Li, Yue Wu, Fei Deng, Dan Yang, Xiao Yang, Renyan Li, Yongzhong Wu, Dongxi Xiang, Tingxiu Xiang   +15 more
wiley   +1 more source

Salvianolic Acid a Disrupts the HSP90α‐AKT‐PERK Ternary Complex to Alleviate Atherosclerosis by Activating Endoplasmic Reticulum Stress of Senescent Vascular Smooth Muscle Cells

Advanced Science, EarlyView.
Salvianolic acid A (SAA) selectively induces senescent vascular smooth muscle cell apoptosis, alleviating atherosclerosis. Mechanistically, SAA targets heat shock protein 90 alpha (HSP90α) to disrupt the protein inase B (AKT)‐PRKR‐Like Endoplasmic Reticulum Kinase (PERK) scaffold, driving ubiquitin‐proteasome‐dependent AKT degradation.
Xiuya Guan, Mengkai Lu, Xinhai Cui, Dawei Zhang, Lei Zhang, Lin Lin, Yuan Li, Yuanlong Hu, Chao Li   +8 more
wiley   +1 more source

Degrading GPX4 via Biomimetic Nanoparticle‐Mediated In Situ Synthesis of Deep‐Learning‐Designed Binder‐Degron Chimeras for Prostate Cancer Therapy

Advanced Science, EarlyView.
A deep‐learning‐designed binder is fused to a combinatorial degron to create a binder‐degron chimera (bdC) that recruits the CUL2‐RING ubiquitin ligase complex. Encapsulation in a prostate‐cancer‐targeted, CD47‐camouflaged nanocarrier enables tumor‐specific in situ bdC expression, triggering GPX4 degradation and ferroptosis, thereby establishing a ...
Si‐Han Zhang, Ye An, Na Zeng, Mei‐Cheng Liu, Jian‐Xuan Sun, Xi Gong, Jin‐Zhou Xu, Shao‐Gang Wang, Qi‐Dong Xia   +8 more
wiley   +1 more source

Developing Metal–Polyphenol Network‐Based Single‐Protein Particle Encapsulation System for Sustained Release of Whey Protein to Mitigate Sarcopenia

Advanced Science, EarlyView.
Sarcopenia has emerged as a major health challenge in the aging population. Developing a sustained‐release system for whey protein may enhance its effectiveness in mitigating sarcopenia. Herein, a novel “single‐protein particle encapsulation” (SPPE) system is developed to protect whey protein and control its release.
Yafei Zhang, Yuning Zhang, Yongjian Ai, Yao Lu, Heng Quan, Zhen Zhang, Yuqi Wang, Yujia Luo, Xiaoxu Zhang, Yingying Lin, Sijia Song, Huiyuan Guo   +11 more
wiley   +1 more source

Lactylation‐Mediated HER2 Stabilization Promotes Trastuzumab Resistance in Gastric Cancer

Advanced Science, EarlyView.
Warburg effect‐derived lactate drives HER2 lactylation and trastuzumab resistance. Mechanistically, AARS1‐mediated lactylation stabilizes HER2 by inhibiting USP11‐dependent degradation and concurrently promotes HER2‐EGFR interaction. Importantly, inhibiting HER2 lactylation resensitizes gastric cancer cells to trastuzumab.
Meng Qian, Tongguan Tian, Zhenxiang Wang, Huihui Sun, Ming Zong, Ying Chen, Jie Xiong, Ye Chen, Zhiqian Hu, Tianming Li, Yanping Xu, Shuchang Xu   +11 more
wiley   +1 more source

AI‐Designed TREM1‐Targeted LYTAC Nanoparticles Reprogram the Neuroimmune Microenvironment in Traumatic Brain Injury

Advanced Science, EarlyView.
AI‐enabled de novo design of a TREM1 binder, integrated into a BBB‐crossing and macrophage‐targeted nanoplatform, enables TREM1 degradation and attenuates neuroinflammation, thereby promoting neuroprotection and tissue repair after traumatic brain injury. ABSTRACT Secondary neuroinflammation drives progressive damage after traumatic brain injury (TBI),
Yimin Huang, Yuan Liu, Huan Peng, Yu Ni, Zhengqiao Jiang, Chenxuan Yu, Xincheng Zhang, Huayu Kang, Yanchao Liu, Juan Chen, Kai Zhao, Lin Han, Xin Zou, Kai Shu, Xiaochuan Wang, Jian‐Zhi Wang, Ting Lei, Chao Gan, Jianfeng Liu, Huaqiu Zhang   +19 more
wiley   +1 more source

Early‐Life Manganese Overexposure Activates Microglial Phagocytosis through the YY1/TREM2 Axis Leading to Hippocampal Synaptic Remodeling in Mice

Advanced Science, EarlyView.
Early‐life manganese exposure induces behavioral deficits and aberrant hippocampal synaptic remodeling by enhancing microglial phagocytosis in young adult male mice. Mechanistically, manganese promotes Yin Yang 1 (YY1)/triggering receptor expressed on myeloid cells 2 (TREM2) signaling through enhanced HIF1α‐mediated transcription and suppressed SMURF2 ...
Keyu Chen, Bin He, Kuan Liu, Zhuo Ma, Bin Xu   +4 more
wiley   +1 more source

USP4‐Dependent CHAF1B Stabilization Regulates Distinct SETDB1 Ubiquitin States Linked to AKT T308 Signaling and Lipogenic Remodeling in HCC

Advanced Science, EarlyView.
USP4 stabilizes CHAF1B by limiting K48‐linked ubiquitination. Stabilized CHAF1B supports UHRF1‐associated K63‐linked SETDB1 ubiquitination and cytoplasmic redistribution, whereas CHAF1B loss favors VHL‐dependent K11‐associated degradative ubiquitination and proteasomal loss of SETDB1.
Saiyan Bian, Yun Tong, Wenkai Ni, Zhangzhi Tang, Weiting Chen, Kexin Ma, Lihan Jiang, Jiayu Shao, Xuyang He, Wenjie Zheng   +9 more
wiley   +1 more source