Results 121 to 130 of about 59,465 (263)

Allosteric Inhibition of Polycomb Repressive Complex 2 by an EZH2‐Selective Small Molecule Inhibitor

Advanced Science, EarlyView.
The study characterizes C36, a highly selective EZH2/PRC2 inhibitor that acts via a novel allosteric mechanism. Unlike previous inhibitors, C36 inhibits EZH2/PRC2 by disrupting the allosteric communication between EZH2 and EED in a SAM‐noncompetitive manner.
Ting Cao, Dongdong Liu, Haishan Gao, Chenyang Qin, Wen Zhang, Ziyun Lu, Dongxia Tan, Yuxiu Qu, Yusong Liu, Zhiran Zou, Hongtao Yu, Wei Qi   +11 more
wiley   +1 more source

PRMT9 Aggravated Dopaminergic Neurodegeneration in Parkinson's Disease Model by Facilitating the Degradation of DUSP26 and Inducing Mitochondrial Dysfunction

Advanced Science, EarlyView.
In the pathological state of PD induced by MPP+, the upregulated PRMT9 in dopaminergic neurons translocates into mitochondrion and interacts with DUSP26 and catalyzes its arginine methylation, leading to the ubiquitin‐proteasomal degradation of DUSP26 mediated by Trim32.
Tengfei Liu, Xiaomeng Song, Xin Guo, Rui Xiao, Ru Sun, Qiuran Ji, Lu Yu, Yiquan Li, Qingyi Fu, Qidi Xue, Lingjun Kong, Lin Chen, Chengjiang Gao, Huiqing Liu   +13 more
wiley   +1 more source

Synergistic HMGN1 and VP64 Fusions Potentiate High‐Precision and PAM‐Flexible Base Editing

Advanced Science, EarlyView.
A novel CDA1Δ‐SpRY architecture fused with HMGN1 and VP64 yields a nearly PAM‐less base editing platform. By focusing cytosine conversion predominantly at position −18, this synergistic complex ensures highly precise targeting. Demonstrating enhanced efficiency across diverse models, including yeast and rice, the platform offers a robust solution for ...
Xi Luo, Yuyao Qu, Zhengyan Ye, Zheng Li, Yuanyan Zhang, Longjiong Luo, Shaokang Li, Wei Zhao, Ming Wang, Ralph Bock, Jianmin Wan, Junjie Tan   +11 more
wiley   +1 more source

E1 Ubiquitin-Activating Enzyme [PDF]

, 2020
openaire   +1 more source

The E3 Ligase RNF115 Aggravates Pathological Cardiac Hypertrophy via Ubiquitin‐Mediated Degradation of SPTBN1

Advanced Science, EarlyView.
In response to hypertrophic stimuli, increased c‑JUN phosphorylation upregulates RNF115, leading to SPTBN1 ubiquitination and degradation. which promotes F‑actin depolymerization and YAP activation, driving cardiac hypertrophy. The RNF115 inhibitor DTD effectively suppresses SPTBN1 ubiquitination and cardiac hypertrophy.
Yan Zu, Shiqing Chen, Ji Chen, Liuliu Ruan, Bowen Li, Weijian Chu, Shichen Huang, Dian Yu, Jing Tian, Yuhan Zhao, Yi Han, Xin Tang, Yong Ji   +12 more
wiley   +1 more source

p300 Degradation by the p53‐SIAH1 Axis Relieves TBK1 Acetylation to Enhance Innate Antiviral Immunity

Advanced Science, EarlyView.
This study identifies p300 as the acetyltransferase that acetylates TBK1 and inhibits its phosphorylation. Activation of the p53‐SIAH1 axis by immune response downregulates p300 expression to sustain innate antiviral immunity. Conditional p300 knockout in alveolar epithelial cells in vivo promotes antiviral responses and suppresses virus replication ...
Huidi Yu, Zhihao Zhan, Xiaoxiang Pan, Xinyue Zhang, Penggang Liu, Jing Sun, Xiulong Xu   +6 more
wiley   +1 more source

ZNF33B Promotes Japanese Encephalitis Virus Infection by Regulating the Stability of M6A‐Modified Trim25 to Control the Autophagy Process

Advanced Science, EarlyView.
Upon JEV infection, ZNF33B recruits METTL14 to stabilize the METTL3‐METTL14 m6A methyltransferase complex, leading to increased m6A modification of host transcripts, including Trim25 mRNA. ZNF33B selectively binds m6A‐modified sites on Trim25 mRNA and accelerates its decay, resulting in reduced TRIM25 protein abundance.
Jian Du, Chunwei Li, Jiyuan Luo, Huizhi Zhang, Jinyan Zhang, Suya Wang, Huanchun Chen, Hongli Xu, Xiangmin Li, Ping Qian   +9 more
wiley   +1 more source

NAD+ Metabolism Licenses Zygotic Genome Activation via PARP7‐Mediated ADP‐Ribosylation of UHRF1 in Mouse Early Embryos

Advanced Science, EarlyView.
This study uncovers a metabolic‐epigenetic axis licensing zygotic genome activation (ZGA) in mouse embryos. A developmental decline in NAD+ levels activates PARP7, which mono‐ADP‐ribosylates and stabilizes UHRF1. This modification promotes the establishment of permissive histone acetylation marks, thereby facilitating timely ZGA.
Guangyi Cao, Ziqi Zhang, Anqi Chen, Yanbo Liu, Yuling Lin, Lina Yu, Ruixin Shi, Aolei Guo, Yan Mao, Ganggui Lou, Chaojun Li, Luhong Wen, Guijun Yan, Haixiang Sun   +13 more
wiley   +1 more source

CHCHD10 Mitigates Alzheimer's Disease‐Related Phenotypes in Association With Epigenetic Remodeling in Directly Reprogrammed Neurons

Advanced Science, EarlyView.
CHCHD10 loss in Alzheimer's disease is associated with mitochondrial dysfunction, epigenomic disruption, and tau pathology. Restoration of CHCHD10 shifts DNA methylation toward a non‐disease state and reduces tau and amyloid pathology, with KATNAL2 acting as a downstream effector.
Teresa M. Thomas, Ching‐Yao Yang, Kexin Zhang, Liam Wetzel, Dina Bugybayeva, Julia Ferguson, Md Mahmudul Hasan, William Samsa, Nandita Patil, Anshul Dash, Tarini Gowda, Xiongwei Zhu, Feixiong Cheng, Tian Liu   +13 more
wiley   +1 more source

UBE2O Drives Immune Evasion and Radioimmunotherapy Resistance in Lung Cancer by Degrading CDKL1 to Induce PD‐L1 Transcription

Advanced Science, EarlyView.
UBE2O targets CDKL1 for the degradation to upregulate PD‐L1 expression and promotes resistance to radioimmunotherapy in lung cancer, supporting the potential of targeting UBE2O as a promising therapeutic strategy. ABSTRACT Resistance to radioimmunotherapy is one of the primary causes of treatment failure in lung cancer patients; however, the underlying
Huichan Xue, Xiaohua Jie, Zhiwei Liu, Ruoxin Fang, Shuo Wu, Xiaorong Dong, Shuangbing Xu   +6 more
wiley   +1 more source