Results 141 to 150 of about 67,820 (304)

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

open access: yesAdvanced 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   +7 more
wiley   +1 more source

Cullin-RING Ubiquitin Ligases in Neurodevelopment and Neurodevelopmental Disorders

open access: yesBiomedicines
Ubiquitination is a dynamic and tightly regulated post-translational modification essential for modulating protein stability, trafficking, and function to preserve cellular homeostasis.
Honoka Ashitomi   +3 more
doaj   +1 more source

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

open access: yesAdvanced 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   +6 more
wiley   +1 more source

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

open access: yesAdvanced 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   +8 more
wiley   +1 more source

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

open access: yesAdvanced 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   +12 more
wiley   +1 more source

ZSL Orchestrates Synaptonemal Complex Assembly as a Central Region Scaffold to Ensure Synapsis Fidelity and Crossover Control in Polyploid Meiosis

open access: yesAdvanced Science, EarlyView.
A central molecular adaptor, ZSL, is identified that links transverse filaments ZYP1 to central element SCEP1/2 to drive synaptonemal complex assembly in Brassica napus. Loss of ZSL abolishes synaptonemal complex formation, disrupts meiotic chromosome segregation, and markedly increases crossovers, providing mechanistic insight into meiotic fidelity ...
Miaowei Geng   +16 more
wiley   +1 more source

ZMAT1 Promotes Osteoclastogenesis Through TRIM46 Mediated YAP1 Degradation and Inhibits Osteoblastogenesis

open access: yesAdvanced 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   +13 more
wiley   +1 more source

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

open access: yesAdvanced 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   +17 more
wiley   +1 more source

BZW1 Drives Immune Evasion in Lung Adenocarcinoma via Ferroptosis Suppression

open access: yesAdvanced Science, EarlyView.
BZW1 attenuates ferroptosis by competitively binding NCOA4 and suppress ferrtinophagy‐mediated iron release. The depletion of BZW1 triggers lipid peroxidation through iron homeostasis. Extracellularly, BZW1 attenuates immunogenic cell death and reinvigorates cytotoxic T‐cell responses.
Linyao Zhao   +9 more
wiley   +1 more source

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