Results 141 to 150 of about 21,465 (238)

Harnessing MDM2‐Mediated Targeted Degradation of Transcriptional and Epigenetic Machinery to Disrupt Oncogenic Addictions in Pediatric Sarcoma

open access: yesAdvanced Science, EarlyView.
MDM2 dependency in pediatric sarcomas is driven by a novel p53‐independent oncogenic cistrome alongside canonical p53 pathway suppression. This study introduces MDM2‐recruiting transcriptional and epigenetic machinery degraders (MDM2‐TEMADs) as a novel precision oncology modality.
Jiawei Zhou   +21 more
wiley   +1 more source

TOLLIP Inhibits Psoriasis Progression via Suppressing PKM2‐Mediated Glycolysis in Keratinocytes

open access: yesAdvanced Science, EarlyView.
In this study, we identify TOLLIP as a critical regulator of psoriasis pathogenesis through its modulation of glycolytic metabolism. Our findings establish the TOLLIP‐PKM2‐glycolysis axis as a key mechanism linking metabolic reprogramming to psoriasis pathogenesis, and propose TOLLIP as a promising therapeutic target.
Xiuhuan Jiang   +11 more
wiley   +1 more source

MEOX1 Coordinates Autocrine‐Paracrine Programs via SPHK1/S1P to Promote Lymph Node Metastasis in Ovarian Cancer

open access: yesAdvanced Science, EarlyView.
In ovarian cancer, MEOX1 activates the SPHK1/S1P pathway to promote both tumor progression and tumor–stroma crosstalk. MEOX1‐dependent signaling drives CAF activation, enhances VEGF‐C expression, and stimulates lymphangiogenesis, ultimately facilitating lymph node metastasis.
Jiajia Li   +10 more
wiley   +1 more source

Dual Cytoplasmic and Chloroplastic Mechanisms Fine‐Tune Chloroplast Division through ARC3 Protein Stability

open access: yesAdvanced Science, EarlyView.
ARC3 levels are controlled by cytosolic and chloroplast proteolytic systems. PUB52 mediates ARC3 precursor ubiquitination and degradation in the cytosol, while CLPC1 promotes ARC3 degradation in chloroplasts, where ARC2 protects ARC3 from excessive breakdown. Disrupting these components causes chloroplast division defects, placing them upstream of ARC3.
Yang Yuan   +5 more
wiley   +1 more source

Loss of E3 Ubiquitin Ligase RINES via CpG Methylation Relieves Suppression of STAT3 and MYC, Facilitating Multiple Tumorigeneses

open access: yesAdvanced Science, EarlyView.
Dysregulated protein modifications drive tumorigenesis. RINES, an E3 ubiquitin ligase, represses tumor cell proliferation and metastasis by facilitating RING domain‐dependent, ubiquitin–proteasome‐mediated degradation of STAT3 and MYC, which consequently restrains cancer stemness and oncogenic progression.
Lili Li   +8 more
wiley   +1 more source

BIN1 and ALDH1B1 Deficiency in Colonic Smooth Muscle Drives Mitochondrial Dysfunction and Fibrosis in Slow‐Transit Constipation

open access: yesAdvanced Science, EarlyView.
Slow‐transit constipation (STC) is a disabling motility disorder with unclear smooth‐muscle mechanisms. Spatial proteomic analysis of STC patient colon reveals both the central pathogenic role of smooth muscle cells (SMCs) in STC and novel regulators of intestinal motility, BIN1 and ALDH1B1.
Jianbo Liu   +10 more
wiley   +1 more source

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