Results 91 to 100 of about 101,514 (215)

REGγ Suppresses Ferroptosis and Induces Drug Resistance by Degrading WDR6 in Chondrosarcoma

open access: yesAdvanced Science, EarlyView.
Here, we identified REGγ as a susceptibility factor in chondrosarcoma. Our study demonstrates that abnormally activated REGγ‐20S proteasome promotes chondrosarcoma development and progression. Further validation in animal models revealed that blocking REGγ function induced ferroptosis, suppressed malignant progression of chondrosarcoma, and uncovered a
Fanrong Liu   +20 more
wiley   +1 more source

ZER1 Restrains Pressure Overload‐Induced Cardiac Remodeling by Targeting DVL2 for Gly/N‐Degron‐Dependent Degradation

open access: yesAdvanced Science, EarlyView.
Pressure overload suppresses cardiomyocyte ZER1, weakening CRL2Zer1‐mediated DVL2 degradation and allowing DVL2 accumulation. Elevated DVL2 activates CaMKII‐HDAC4‐MEF2C signaling, drives fetal gene reactivation, and promotes pathological remodeling.
Mingchao Jiang   +27 more
wiley   +1 more source

Integrative Omics Analysis Reveals the Regulation of Hypoxia Tolerance in Large Yellow Croaker (Larimichthys crocea) via the Lipoic Acid Synthase (lias) Gene

open access: yesAdvanced Science, EarlyView.
Lipoic acid synthase (lias) can regulate α‐KG levels through lipoylation, thereby negatively regulating HIF‐1α protein levels via PHD under hypoixa. The Hap2 allele of lias exhibits lower expression levels than Hap1, leading to the accumulation of more HIF‐1α protein and thereby enhancing hypoxia tolerance. ABSTRACT Hypoxia stress seriously affects the
Jie Ding   +7 more
wiley   +1 more source

Molecular and Cellular Hallmarks of Age‐Related Vestibular Hair Cell Degeneration

open access: yesAdvanced Science, EarlyView.
This study utilizes single‐cell RNA‐seq transcriptomes, advanced imaging, and electrophysiology to examine universal and cell‐type‐specific aging signatures of vestibular hair cells. The study shows that impaired hair bundle function is a key driver of age‐related vestibular dysfunction.
Samadhi Kulasooriya   +10 more
wiley   +1 more source

MAM‐Localized MANF Counteracts Microinflammatory Stress to Attenuate Mitochondrial Dysfunction and Cataractogenesis in High Myopia

open access: yesAdvanced Science, EarlyView.
Chronic microinflammation in high myopia suppresses MANF in lens epithelial cells. MANF normally resides within MAMs and promotes ubiquitin‐mediated degradation of the ER Ca2+ pump SERCA2. MANF loss causes pathological SERCA2 accumulation, MAM hyperassembly, and disrupted ER‐to‐mitochondria Ca2+ transfer, leading to mitochondrial failure, oxidative ...
Xin Liu   +8 more
wiley   +1 more source

PRMT5‐Dependent Stabilization of VPS34 Orchestrates Copper Trafficking to Shield Cancer Cells from Cuproptosis and Radiotherapy

open access: yesAdvanced Science, EarlyView.
Radioresistance arises partly from tumor cells evading cuproptosis via unknown defenses. This study reveals that the PRMT5‐VPS34 axis acts as a radiation‐activated anticuproptotic mechanism: PRMT5 methylates VPS34 at Arg174, recruiting USP10 to remove K48‐linked ubiquitination and prevent degradation.
Wei Chen   +17 more
wiley   +1 more source

Porcine Deltacoronavirus M Protein Binds NLRP3 to Promote Inflammasome Assembly via Competition with TRIM31

open access: yesAdvanced Science, EarlyView.
Porcine deltacoronavirus (PDCoV) infection induces severe intestinal inflammation and acute diarrhea in piglets, yet the molecular mechanism remains incompletely understood. The M protein activates NLRP3 inflammasome through dual mechanisms: direct binding to the NLRP3 LRR domain and disruption of TRIM31‐mediated K48‐linked ubiquitination.
Jinhui Hou   +11 more
wiley   +1 more source

Psychological Stress Associated Bile Acid Reprogramming Promotes Hepatocellular Carcinoma Progression

open access: yesAdvanced Science, EarlyView.
Depression is increasingly recognized as a risk factor for chronic diseases, yet its biological impact on cancer remains unclear. Using data from more than 490 000 participants across three international cohorts, we show that depression significantly increases the risk of liver cancer.
Ruijiang Zeng   +10 more
wiley   +1 more source

PFKFB4 Deubiquitination by USP10 Enhances Fumarate Metabolism to Orchestrate the KDM1A/Rad51 Axis and Confer Radioresistance in Lung Cancer

open access: yesAdvanced Science, EarlyView.
USP10 binds to and stabilizes PFKFB4, enhancing glycolytic ATP production, which activates the urea cycle and elevates fumarate. This inhibits histone demethylase KDM1A, leading to increased H3K4me1 enrichment at the Rad51 promoter and direct activation of Rad51 transcription, which confers lung cancer radioresistance. The PFKFB4 inhibitor 5MPN targets
Yunshang Chen   +7 more
wiley   +1 more source

TP53 R249S mutation in hepatic organoids captures the predisposing cancer risk

open access: yesHepatology, EarlyView., 2022
The systematic approach in elucidating the gain‐of‐function (GOF) roles of TP53 mutations in early liver carcinogenesis. Unique downstream targets of TP53 L3 mutations were identified from chormatin immunoprecipitation sequencing in HCC cell lines, followed by a series of validation assays to substantiate the exclusive transcriptional regulations ...
Yin Kau Lam   +10 more
wiley   +1 more source

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