Results 91 to 100 of about 47,607 (250)

E3 ubiquitin ligases in signaling, disease, and therapeutics

Trends in Biochemical Sciences
The ubiquitin-proteasome system (UPS) is a central regulator of protein turnover and signaling, with E3 ubiquitin ligases conferring substrate specificity and chain-type control. Recent advances have revealed new mechanistic classes of E3 ligases and expanded our understanding of their roles in disease, including cancer, neurodegeneration, and immune ...
Pirouz Ebadi, Caleb M. Stratton, Shaun K. Olsen   +2 more
openaire   +2 more sources

IKKβ and USP28 Regulate HEY1 Stability to Promote Cancer Stemness and Immune Evasion in Hepatocellular Carcinoma

Advanced Science, EarlyView.
The uncovered IKKβ‐USP28‐HEY1 axis fuels cancer stemness and immune evasion in hepatocellular carcinoma. USP28 deubiquitinates HEY1 upon IKKβ‐mediated phosphorylation, conferring PD‐1/PD‐L1 blockade resistance. Pharmacological inhibition of USP28 sensitizes resistant tumors to anti‐PD‐1 immunotherapy, revealing a promising therapeutic strategy ...
Na Shao, Lin Zhang, Gufang Shen, Yangfan Lv, Tianshu Fang, Ya Cao, Qiongyi Zhang, Feng Xu, Chungang Liu   +8 more
wiley   +1 more source

A multi-lock inhibitory mechanism for fine-tuning enzyme activities of the HECT family E3 ligases

Nature Communications, 2019
HECT type E3 ligases are key regulators of cell growth and proliferation. Here the authors present the crystal structures of the Nedd4 family E3 ligase WWP1 in a closed and semi-open state and in combination with mutagenesis experiments identify a multi ...
Zhen Wang, Ziheng Liu, Xing Chen, Jingyu Li, Weiyi Yao, Shijing Huang, Aihong Gu, Qun-Ying Lei, Ying Mao, Wenyu Wen   +9 more
doaj   +1 more source

mTORC2 Phosphorylation of GSDME‐N Drives Cullin4B‐Mediated Proteasomal Degradation to Suppress Pyroptosis and Confer Radioresistance in Small Cell Lung Cancer

Advanced Science, EarlyView.
Radioresistance severely limits the efficacy of therapies for small cell lung cancer (SCLC). This study reveals a novel mechanism of resistance driven by the active suppression of pyroptosis. Specifically, the mTORC2 complex directly phosphorylates GSDME‐N and promotes its CUL4B‐mediated ubiquitination and proteasomal degradation.
Qing‐qing Xu, Ci‐ming Sun, Sui‐xian Zhang, Rui Li, Chen‐fei Wu, Zai‐shan Lin, Li Li, Run‐zhe Chen, Qi‐wen Li, Yuan‐yuan Chen, Xuan Li, Ming Chen   +11 more
wiley   +1 more source

PDIA6–SCD1 Axis Rewires Lipid Metabolism to Drive Gastric Cancer Progression

Advanced Science, EarlyView.
Protein disulfide isomerase A6 (PDIA6) is identified as an oncogenic driver in gastric cancer. PDIA6 directly binds and stabilizes SCD1 by limiting its ubiquitin–proteasome‐mediated degradation, thereby sustaining monounsaturated fatty acid (MUFA)‐enriched lipid homeostasis and lipid metabolic reprogramming.
Zhen Tian, Yifan Cheng, Jiajie Zhou, Ruiqi Li, Shuai Zhao, Ben Li, Zijie Xu, Mengli Zi, Yayan Fu, Chenkai Zhang, Qiannan Sun, Shantanu Baral, Sen Wang, Daorong Wang   +13 more
wiley   +1 more source

E3 ubiquitin ligases: key regulators of osteogenesis and potential therapeutic targets for bone disorders

Frontiers in Cell and Developmental Biology
Ubiquitination is a crucial post-translational modification of proteins that mediates the degradation or functional regulation of specific proteins. This process participates in various biological processes such as cell growth, development, and signal ...
Heng-Rui Zhang, Heng-Rui Zhang, Yang-Hao Wang, Yang-Hao Wang, Zhen-Ping Xiao, Zhen-Ping Xiao, Guang Yang, Yun-Rong Xu, Zai-Tian Huang, Wei-Zhou Wang, Fei He   +10 more
doaj   +1 more source

RNF138‐Mediated Ubiquitination and Degradation of NS5 Restricts Tick‐Borne Encephalitis Virus Infection

Advanced Science, EarlyView.
Host‐specific compatibility between RNF138‐like proteins and flavivirus NS5 determines NS5 stability. Mammalian RNF138 but not arthropod homologs recognizes and induces conserved NS5/RdRp K48‐linked ubiquitination and proteasomal degradation, thereby restricting viral replication. Ectopic RNF138 in mice attenuates TBEV‐induced pathogenesis. (Created in
Jialiang Sun, Weijing Yang, Hao Zhou, Shuai Li, Xin Jiang, Jianyang Gu, Wenyan Zhang   +6 more
wiley   +1 more source

The role of HECT-type E3 ubiquitin ligases in inflammation

Frontiers in Immunology
Homologous to the E6-AP Carboxyl Terminus (HECT)-type E3 ubiquitin ligases are key components of the ubiquitin-proteasome system (UPS) and play an important role in the regulation of inflammatory responses. Inflammation serves as a core defense mechanism
Ziyi Wang, Peirui Wang, Huawang Xie, Zhibo You, Xiping Liu, Fang Cao, Shengtao Yao   +6 more
doaj   +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

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