Results 111 to 120 of about 98,327 (230)

The ITGB2‐COPS3‐SOX2 Axis and SOX2 Liquid‐Liquid Phase Separation: Dual Mechanisms Governing Osteosarcoma Stemness

Advanced Science, EarlyView.
Osteosarcoma stemness is driven by the ITGB2‐COPS3‐SOX2 signaling axis. This study reveals that nuclear COPS3 stabilizes SOX2, which in turn undergoes liquid‐liquid phase separation to promote stemness. Based on this mechanism, a novel COPS3 inhibitor, Z‐5891, was developed, effectively suppressing tumor growth and stemness in vivo, offering a ...
Lei Guo, Zhiqing Zhao, Wei Wang, Jianfang Niu, Bing Wang, Yunfei Lin, Wei Guo, Taiqiang Yan   +7 more
wiley   +1 more source

Dual Aptamers‐Based SETDB1 PROTACs as Effective Anti‐Tumor Strategies for Breast Cancer

Advanced Science, EarlyView.
This study establishes dual‐aptamer PROTACs targeting SETDB1 using a SETDB1‐specific aptamer conjugated to AS1411. The designed PROTACs penetrate cells, recruit MDM2 to degrade SETDB1, and inhibit cancer cell proliferation and migration. Remarkably, they also overcome tamoxifen resistance and enhance CD8+ T cell cytotoxicity, suppressing tumor growth ...
Yanxuan Guo, Yingge Lv, Shuyu Huang, Chang Liu, Yan Ouyang, Bei Lan, Chenghao Xuan   +6 more
wiley   +1 more source

Phosphatidic Acid‐TRIM59‐Olig2 Signaling Couples Metabolic Dysfunction to Myelination Failure in PWMI

Advanced Science, EarlyView.
PA accumulates after hypoxic‐ischemic injury and stabilizes the E3 ligase TRIM59 in OPCs. Stabilized TRIM59 enhances ubiquitination and degradation of Olig2, blocking differentiation and causing hypomyelination in PWMI. Modulating PA synthesis restores Olig2 levels, improves myelination, and ameliorates behavioral deficits, defining a metabolically ...
Xinyu Li, Yanan Liu, Meng Zhang, Yiwei Liu, Meiting Liu, Kaishen Zhu, Zhian Liu, Chao Ren, Ruiqin Yao   +8 more
wiley   +1 more source

TRIM40 Drives Pathological Cardiac Hypertrophy and Heart Failure via Ubiquitination of PKN2

Advanced Science, EarlyView.
This study identifies the E3 ligase TRIM40 as a key driver of pathological cardiac hypertrophy. TRIM40 binds PKN2 via its B‐box domain and, through its C29‐dependent catalytic activity, mediates K63‐linked ubiquitination of PKN2. This modification enhances PKN2 phosphorylation at Ser815, thereby driving hypertrophy.
Risheng Zhao, Xiaoli Cui, Huizhu Du, Zhuoqun Wang, Chang Liu, Linxin Zhang, Jianing Qi, Di Yang, Hui Yu, Shuang Yan, Wei Liu, Haiming Sun, Mengyang Wang   +12 more
wiley   +1 more source

Loss of VMP1 Impairs Tight Junction Recycling and Aggravates Intestinal Barrier Dysfunction in Inflammatory Bowel Disease

Advanced Science, EarlyView.
This study identifies vacuole membrane protein 1 (VMP1) as a critical regulator of intestinal epithelial barrier homeostasis. VMP1 facilitates the recruitment of CORO1C to late endosomes, supporting Retromer‐mediated recycling of the tight junction protein Occludin.
Jiawei Zhao, Jianjun Zou, Chen Zhou, Yingui Wang, Yiman Liu, Yanqing Zhou, Yuxiang Wang, Xinyu Zhang, Huishu Yang, Hongjie Yin, Dongsheng Bai, Yue Zhao, Na Lu   +12 more
wiley   +1 more source

ZMAT1 Promotes Osteoclastogenesis Through TRIM46 Mediated YAP1 Degradation and Inhibits Osteoblastogenesis

Advanced Science, EarlyView.
Zmat1 deficiency mitigates pathological bone loss by impairing osteoclastogenesis and promoting osteoblastogenesis. Mechanistically, in osteoclasts, Zmat1 loss relieves transcriptional repression of the E3 ligase TRIM46, promoting YAP1 degradation and inhibiting osteoclastogenic genes.
Xinyu Chang, Yijin Hou, Likun Cui, Huiqi Yu, Rong Liu, Junhao Sui, Zhong Zheng, Lu Liu, Jie Chen, Mengchen Chen, Chen Ding, Shuogui Xu, Sheng Xu, Hao Zhang   +13 more
wiley   +1 more source

Artesunate Ameliorates APAP‐induced Liver Injury by Promoting NEDD4L‐Mediated Ubiquitination and Degradation of TXNIP

Advanced Science, EarlyView.
ABSTRACT Liver injury can lead to severe acute liver failure and even death in patients. Artesunate (ART), which is a derivative of artemisinin that has been approved by the FDA for the treatment of malaria, has significant regulatory effects on cell death and inflammation.
Zhe Zhang, Hongyi Zhang, Haixiang Guo, Xiwen Zhang, Yidan Wang, Baoyin Wang, Tong Wang, Guokun Zhao, Qing Zhang, Fei Gao, Shuang Liang, Hao Jiang, Yu Ding, Xiliang Du, Jiabao Zhang, Yi Zheng, Xinwei Li, Bao Yuan   +17 more
wiley   +1 more source

Promoter Hypermethylation‐Induced Silencing of FXYD1 Drives Breast Cancer Metastasis via DDX5‐Mediated Wnt/β‐Catenin Pathway Activation

Advanced Science, EarlyView.
This study identifies FXYD1 as an epigenetically silenced tumor suppressor in breast cancer. DNA methylation turns off the gene FXYD1 in breast cancer, and low levels predict worse outcomes. Restoring FXYD1 limits breast cancer cells proliferation and metastasis. In the nucleus, FXYD1 recruits the E3 ligase MAEA to K63‐ubiquitinate DDX5 for proteasomal
Ping Wen, Fanli Qu, Long Wang, Qing Shao, Sisi Li, Yang Qin, Dongping Jiang, Senmiao Zhang, Jiangdong Sui, Guanwen Wang, Ningning Zhang, Xiaohua Zeng   +11 more
wiley   +1 more source

Ubiquitin proteasome system and myopathies

, 2015
Ziel Idiopathische inflammatorische Myopathien (IIM) sind gekennzeichnet durch die Infiltration von Immunzellen in den Muskel und eine erhöhte MHC-I-Expression. Dies lässt auf eine erhöhte Antigenpräsentation und Beteiligung des Proteasom-Systems schließen.
openaire   +1 more source

TrxR2 Lactylation Facilitates Mitochondrial Protection and Endothelial Ferroptosis Resistance in Diabetic Cardiomyopathy

Advanced Science, EarlyView.
TrxR2 deletion in diabetic mice suppresses TUFM‐AMPK‐FUNDC1‐dependent mitophagy in endothelial cells, resulting in SCP2 upregulation and mitochondrial translocation of ACSL4. Mitochondrial ACSL4 promotes mitochondrial eicosanoid biosynthesis and ferroptosis, thereby aggravating cardiac microvascular injury and diabetic cardiomyopathy.
Su Li, Muyin Liu, Chao Chen, Xinyan Li, Xiaopei Yan, Wentao Zhu, Wenyan Qiu, Qiyu Li, Xiangyu Sun, Chao Huang, Ming Yin, Zhangwei Chen, Yao Lu, Junbo Ge, Xiangqing Kong, Juying Qian, Yuqiong Chen   +16 more
wiley   +1 more source