Results 161 to 170 of about 2,792 (256)

Matrix Stiffness Orchestrates Mesenchymal Stem Cell Lineage Commitment Toward Osteogenesis and Adipogenesis Through the PIEZO1/SP1/STC2 Axis

open access: yesAdvanced Science, EarlyView.
Matrix stiffness directs mesenchymal stem cell lineage commitment through PIEZO1‐dependent activation of the SP1/STC2 pathway. Stiff matrices favor osteogenesis and suppress adipogenesis, whereas the loss of PIEZO1 function impairs early bone formation. STC2 retains lineage‐regulatory activity even when PIEZO1 is inactive.
Shuo Zhang   +12 more
wiley   +1 more source

Uhrf1‐Mediated PKM2 Degradation via Ubiquitination Alleviates Inflammation and Pyroptosis in Inflammatory Bowel Disease

open access: yesAdvanced Science, EarlyView.
Uhrf1‐mediated PKM2 ubiquitination and degradation repressed the nuclear translocation of PKM2, and EPT served as a molecular glue capable of targeting the Uhrf1–PKM2 complex to alleviate the IBD course, suggesting that the Uhrf1–PKM2 axis was a previously unrecognized strategy for treating IBD.
Juan Zhang   +9 more
wiley   +1 more source

Macrophage RSAD2 Couples mtDNA Synthesis With a Self‐Amplifying Inflammatory Circuit to Orchestrate Tissue Repair

open access: yesAdvanced Science, EarlyView.
Macrophage RSAD2 dually regulates CMPK2—the rate‐limiting enzyme for mitochondrial DNA synthesis—by suppressing its ubiquitination and promoting its phosphorylation via Csnk2a2 recruitment. This amplifies mtDNA production, which simultaneously activates a cGAS‐STING‐IRF3‐RSAD2 feedforward loop and the NLRP3 inflammasome, driving a self‐sustaining ...
Haomiao Yuan   +16 more
wiley   +1 more source

Impaired Chaperone‐Mediated Autophagy Accelerates Intervertebral Disc Degeneration by Inducing MIDN Accumulation to Target TSC2 for Proteasomal Degradation

open access: yesAdvanced Science, EarlyView.
This graphical abstract illustrates how chaperone‐mediated autophagy (CMA) regulates intervertebral disc degeneration (IDD). Under normal homeostasis (B), CMA degrades cytoplasmic Midnolin (MIDN) to maintain proteostasis. Under inflammatory stress (A), impaired CMA leads to cytoplasmic MIDN accumulation.
Xianglong Chen   +9 more
wiley   +1 more source

Natural Product Toosendanin Suppresses the Malignant Development of Skin Melanoma by Targeting BNC2 for Degradation

open access: yesAdvanced Science, EarlyView.
BNC2 exhibits context‐dependent opposing functions across multiple cancer types. This study reveals BNC2 as an oncogenic driver of melanoma proliferation and metastasis through transcriptional activation of PIK3CA. The natural compound TSN simultaneously degrades BNC2 and its oncogenic partner SMAD3 via CRBN‐dependent ubiquitination.
Hui Dai   +7 more
wiley   +1 more source

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