Results 171 to 180 of about 51,947 (207)

VCP‐Regulated LMF2 Stabilizes the Cholesterol Biosynthesis Enzyme HMGCS1 to Drive Cancer Progression and Confer Capecitabine Resistance in Triple‐Negative Breast Cancer

open access: yesAdvanced Science, EarlyView.
LMF2 drives progression and capecitabine resistance in triple‐negative breast cancer (TNBC). Mechanistically, VCP prevents NBR1‐mediated autophagic degradation of LMF2, thereby stabilizing it. Stabilized LMF2 subsequently suppresses NDP52‐mediated autophagic degradation of HMGCS1, a rate‐limiting cholesterol biosynthesis enzyme.
Qian Zhao   +12 more
wiley   +1 more source

Mitochondrial Quality Control in Degenerative Musculoskeletal Diseases: Signaling Networks and Therapeutic Landscapes

open access: yesAdvanced Science, EarlyView.
Mitochondrial quality control (MQC) collapse redefines osteoarthritis, intervertebral disc degeneration, and osteoporosis as disorders of organelle dysfunction. Damaged mitochondria leak mtDNA and metabolites, driving cGAS‐STING inflammation, epigenetic reprogramming, and metabolic memory.
Haiyang Gao   +7 more
wiley   +1 more source

Tubocapsenolide A Overcomes Oxaliplatin Resistance in Colorectal Cancer by Targeting PLK1 to Impair CEP55–ESCRT‐Associated Vesicular Damage Clearance

open access: yesAdvanced Science, EarlyView.
Oxaliplatin‐resistant colorectal cancer cells utilize a previously unappreciated PLK1‐CEP55‐ESCRT‐driven vesicular extrusion mechanism to clear L‐OHP‐induced cellular damage. The natural withanolide Tubocapsenolide A directly targets and inhibits PLK1 to disrupt this specific damage‐clearance machinery. This blockade induces severe nucleolar stress and
Yueying Yang   +15 more
wiley   +1 more source

HECTD1 Directs HIF‐1α to Facilitate Intestinal Inflammation and Carcinogenesis via Promoting Th17 Differentiation and Glycolysis

open access: yesAdvanced Science, EarlyView.
HECTD1 emerges as an upstream amplifier of Th17 metabolic programming by promoting K63‐linked ubiquitination of IGF2BP3 and enhancing HIF‐1α translation. HIF‐1α reciprocally drives HECTD1 transcription, establishing a positive regulatory loop that sustains glycolysis and Th17 differentiation.
Shuiyu Xu   +12 more
wiley   +1 more source

Donor‐Cell Senescence Redirects PINK1‐Marked Mitochondrial Cargo From Mitophagy to Microvesicle Transfer Through SUMO3‐Stabilized HSPA9

open access: yesAdvanced Science, EarlyView.
ABSTRACT Extracellular vesicle therapies have been developed for tissue repair, but how donor‐cell senescence reshapes vesicle‐mediated mitochondrial transfer remains unclear. Here, we show that senescent adipose‐derived stem cells (ADSCs) redirect damaged mitochondria into microvesicles (MVs), converting protective vesicles into pro‐degenerative ...
Zixuan Ou   +21 more
wiley   +1 more source

Astrocytic Ketogenesis Protects Central Nervous System Injury via CPT1A Stabilization and Epigenetic Regulation

open access: yesAdvanced Science, EarlyView.
A distinct astrocyte subpopulation, enriched at the lesion border, drives CNS repair through enhanced ketone body metabolism. This process promotes neuronal survival and axonal sparing via CPT1A stabilization and H3K9bhb‐dependent epigenetic reprogramming, positioning astrocytic ketogenesis as a promising therapeutic target for tissue regeneration ...
Dishui Pan   +14 more
wiley   +1 more source

ALDH2 Suppresses Ferroptosis and Promotes Bortezomib Resistance in Multiple Myeloma Through the KEAP1‐NRF2 Feedback Loop

open access: yesAdvanced Science, EarlyView.
ALDH2, which is overexpressed in multiple myeloma, competitively binds KEAP1 to stabilize NRF2 by blocking its ubiquitin‐proteasomal degradation. Stabilized NRF2 translocates into the nucleus to upregulate the expression of GPX4. In parallel, NRF2 binds to the ALDH2 promoter to regulate its transcription, forming a positive feedback loop that represses
Ruonan Shao   +10 more
wiley   +1 more source

CaMKIIδ Phosphorylates AUP1 to Promote Pancreatic Tissue Repair and Acinar‐to‐Ductal Metaplasia Formation via Mediating PERK‐Dependent Unfolded Protein Responses

open access: yesAdvanced Science, EarlyView.
CaMKIIδ–AUP1 signaling maintains PERK‐dependent ER homeostasis during ADM‐mediated pancreatic repair. ABSTRACT Pancreatic repair after acute pancreatitis (AP) is essential for restoring tissue integrity, but the intrinsic mechanisms coordinating acinar plasticity and regeneration remain poorly understood.
Yonghao Chen   +10 more
wiley   +1 more source

Melatonin Mitigates Doxorubicin‐Induced Cardiotoxicity by Targeting the USP18/PKM2 Axis Without Compromising Antitumor Efficacy

open access: yesAdvanced Science, EarlyView.
Melatonin engages MT1/MT2 receptors to suppress STAT1‐driven USP18 upregulation, thereby redirecting PKM2 ubiquitination from K33‐linked autophagic degradation toward K27‐linked nuclear translocation. This prevents PKM2‐mediated proinflammatory gene expression in the heart, alleviating doxorubicin‐induced cardiotoxicity without compromising antitumor ...
Zhenyu Feng   +10 more
wiley   +1 more source

The VCPIP1‐UBE3A Deubiquitination‐Ubiquitination Cascade Contributes to Castration‐Resistant Prostate Cancer Progression

open access: yesAdvanced Science, EarlyView.
VCIPIP1 emerges as a molecular link between protein stability and prostate cancer progression. By deubiquitinating and stabilizing UBE3A, VCIPIP1 promotes p53 degradation and progression to castration‐resistant prostate cancer. Elevated VCIPIP1 expression is associated with shorter castration‐resistant prostate cancer–free survival, highlighting the ...
Fei Lin   +9 more
wiley   +1 more source

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