Results 101 to 110 of about 47,588 (257)

SR‐A3 Promotes USP18‐Mediated deISGylation of STING to Protect Against Myocardial Ischemia‐Reperfusion Injury

open access: yesAdvanced Science, EarlyView.
MI/RI is a major clinical challenge with high morbidity and mortality. This study demonstrates that SR‐A3 expression is downregulated in MI/RI, and its deletion exacerbates damage via the USP18/ISG15/STING axis, revealing SR‐A3 as a potential therapeutic target.
Yufei Han   +24 more
wiley   +1 more source

A New Recruitable E3 Ligase UHRF1 Supporting Targeted Protein Degradation: A Minimal Azide as a Recruitment Ligand

open access: yesAdvanced Science, EarlyView.
Targeted protein degradation is often limited by the scarcity of usable E3 ligases. Herein, we report the first small‐molecule GPX4 degraders that incorporate either electrophilic warheads or a minimal azide group as an E3 recruitment ligand. The azide‐based degrader DK‐5070 effectively drives potent GPX4 degradation; mechanistic studies reveal that ...
Zehong Lin   +14 more
wiley   +1 more source

SPARC Drives Podocyte Mitochondrial Damage and Ferroptosis in Diabetic Kidney Disease Following Klotho Deficiency

open access: yesAdvanced Science, EarlyView.
Klotho deficiency promotes podocyte mitochondrial dysfunction and ferroptosis through activation of the PKCα/CUX1/SPARC/TGFβ‐RII axis. SPARC emerges as a key mediator linking Klotho loss to podocyte injury in DKD and other kidney injury models, suggesting broader implications for CKD progression.
Qing Yang   +11 more
wiley   +1 more source

Photobiomodulation‑Engineered Extracellular Vesicles Enhance Neural Differentiation via UFL1‑Mediated UFMylation in Spinal Cord Injury

open access: yesAdvanced Science, EarlyView.
Photobiomodulated microglia release engineered extracellular vesicles that deliver UFL1 to the injured spinal cord. UFL1 competitively binds p53 with MDM2, inhibiting p53 ubiquitination and stabilizing p53 signaling. This dual mechanism simultaneously promotes anti‐inflammatory microglial polarization and directs neural stem cell differentiation toward
Yunxiao Fang   +12 more
wiley   +1 more source

Phase Separation of TRIM21 Modulates PTPN14 Stability to Drive Flow‐Dependent Endothelial Activation and Atherogenesis

open access: yesAdvanced Science, EarlyView.
Disturbed flow promotes the formation of TRIM21‐rich biomolecular droplets, which concentrate TRIM21 and PTPN14 and facilitate their SPRY‐FERM interaction (illustrated by the TRIM21 D355‐PTPN14 R132 salt bridge). This condensate‐driven proximity enables TRIM21 to catalyze K48‐linked polyubiquitination of PTPN14 at lysine 956, leading to proteasome ...
Xue He   +10 more
wiley   +1 more source

Loss of CYLD on Chromosome 16q Impairs Homologous Recombination and Genomic Stability Through TIRR Degradation

open access: yesAdvanced Science, EarlyView.
Chromosome 16q loss drives genomic instability through disruption of the CYLD–TIRR–53BP1 axis. CYLD preserves homologous recombination by stabilizing TIRR and limiting 53BP1 accumulation at DNA double‐strand breaks. CYLD deficiency redirects repair toward error‐prone non‐homologous end joining, promotes mutational burden and homologous recombination ...
Mingming Lu   +14 more
wiley   +1 more source

Targeting E3 Ubiquitin Ligases for Cancer Therapy

open access: yesCancer Biology & Therapy, 2003
E3 ubiquitin ligases are a large family of proteins that can be classified into three major structurally distinct types: N-end rule E3s, E3s containing the HECT (Homology to E6AP C-Terminus) domain, and E3s with the RING (Really Interesting New Gene) finger, including its derivatives, the U- Box and the PHD (Plant Homeo-Domain).
openaire   +2 more sources

An Effector TaCRVP From Tuta Absoluta Oral Secretion Impairs H2O2‐Mediated Plant Defense by Targeting Tomato SlCAT2

open access: yesAdvanced Science, EarlyView.
The Tuta absoluta salivary effector TaCRVP subverts tomato immunity by hijacking host catalase SlCAT2. Through a sophisticated dual mechanism, TaCRVP simultaneously promotes SlCAT2 tetramerization for activation and blocks its SlAdBiL‐mediated degradation for stabilization.
Jianquan Yan   +9 more
wiley   +1 more source

Autophagy Orchestrates Anti‐Tumor Immunity to Enhance Chemosensitivity via the FBXW2/C/EBPβ/TIMP‐2 Axis in Colorectal Cancer

open access: yesAdvanced Science, EarlyView.
Chemotherapy leverages tumor‐cell autophagy to reshape the colorectal cancer immune microenvironment. Autophagy degrades FBXW2 to promote C/EBPβ‐mediated TIMP‐2 transcription and MMP‐9 suppression, driving intra‐tumoral CD8+ T‐cell infiltration. Targeting MMP‐2/9 or restoring TIMP‐2 overcomes chemo‐resistance in autophagy‐deficient tumors. ABSTRACT The
Bing Cheng   +12 more
wiley   +1 more source

GSTM4 Suppresses Prostate Cancer Progression by Targeting TRIM27‐mediated ACLY Ubiquitination and Lipid Metabolism

open access: yesAdvanced Science, EarlyView.
GSTM4 enhances the interaction between ACLY and the E3 ubiquitin ligase TRIM27, thereby increasing K48‐linked ubiquitination at the K554 site of ACLY and promoting its degradation. Consequently, GSTM4 regulates lipid synthesis, as well as the proliferation and metastasis of PCa cells, by modulating ACLY stability.
Kang‐Ping Xiong   +11 more
wiley   +1 more source

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