Results 211 to 220 of about 248,818 (307)

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

Lactate‐Induced K370 Lactylation of STING Inhibits STING‐TBK1 Signaling and Dampens Anti‐Tumor Immunity

open access: yesAdvanced Science, EarlyView.
Lactate accumulation in glioblastoma drives lactylation of STING at lysine 370, a primate‐conserved residue. K370 lactylation weakens STING‐TBK1 binding, destabilizes STING, and disrupts ER‐to‐Golgi trafficking, blunting type I interferon signaling. LDHA inhibition reverses K370 lactylation and improves the antitumor efficacy of STING agonism combined ...
Yueyao Wu   +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

Comparative analysis of neuronal proteolytic pathways reveals neuron-specific and sub-compartmental-specific capacities with aging. [PDF]

open access: yesCell Mol Life Sci
Sleiman M   +10 more
europepmc   +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

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