Results 121 to 130 of about 67,820 (304)

UBE2T‐Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation‐Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
This study integrates multi‐omics to reveal the critical role of UBE2T in driving malignancy and stromal co‐evolution in PDAC. UBE2T potentiates glycolysis by regulating p53 degradation via a positive feedback loop, thereby promoting histone H3 lysine 18 lactylation in CAFs and stromal deposition. The UBE2T inhibitor PGG represents a potential strategy
Yong Ma   +16 more
wiley   +1 more source

Discovery of SKP2‐Recruiting PROTACs for Target Protein Degradation

open access: yesAdvanced Science, EarlyView.
Based on the SKP2‐targeting ligand SL1, we designed non‐covalent PROTACs by linking it with the BRD4 inhibitor JQ1 and the AR antagonist AL through a linker. These PROTACs successfully induced the ubiquitination of BRD4 and AR, followed by proteasome‐mediated degradation.
Guanjun Dong   +13 more
wiley   +1 more source

Targeting Lactate and Lactylation in Cancer Metabolism and Immunotherapy

open access: yesAdvanced Science, EarlyView.
Lactate, once deemed a metabolic waste, emerges as a central regulator of cancer progression. This review elucidates how lactate and its epigenetic derivative, protein lactylation, orchestrate tumor metabolism, immune suppression, and therapeutic resistance.
Jiajing Gong   +5 more
wiley   +1 more source

The novel E3 ligase of PPAR?? TRIM25 regulates adipocyte differentiation [PDF]

open access: yes, 2018
Department of Biological SciencesPeroxisome proliferator-activated receptor ?? (PPAR??) is a ligand-dependent transcription factor which regulates glucose homeostasis and adipocyte differentiation.
Lee, Jae Min
core  

An Insulin‐Exosome‐TNFAIP8 Axis Drives Stromal Fibrosis and Therapeutic Resistance in Pancreatic Cancer

open access: yesAdvanced Science, EarlyView.
In pancreatic ductal adenocarcinoma (PDAC), insulin is associated with activation of PI3K/AKT–RAB3A signaling and enhanced secretion of TNFAIP8‐enriched exosomes from tumor cells. Uptake of these exosomes by fibroblasts is linked to TRIM21‐dependent STAT1 degradation and the emergence of myofibroblastic CAF–associated features, accompanied by increased
Zhenyu Li   +15 more
wiley   +1 more source

F‐Box and Leucine‐Rich Repeat Protein 4 (FBXL4) Maintains Sarcomere Integrity and Cardiac Function by Enhancing K48‐Linked Ubiquitinated Degradation of Profilin‐1 (PFN1)

open access: yesAdvanced Science, EarlyView.
Schematic diagram depicting the proposed signaling mechanisms underlying the effects of FBXL4 in the setting of cardiac hypertrophy. Under hypertrophic stimulation, cardiomyocytes‐specific overexpression FBXL4 maintains sarcomere integrity and cardiac function by enhancing K48‐linked ubiquitinated degradation of PFN1 at the K70 site.
Xingda Li   +11 more
wiley   +1 more source

A Tobacco Homolog of DCN1 is Involved in Cellular Reprogramming and in Developmental Transitions [PDF]

open access: yes, 2011
Plant proteomes show remarkable plasticity in reaction to environmental challenges and during developmental transitions. Some of this adaptability comes from ubiquitin-mediated protein destruction regulated by cullin-RING E3 ubiquitin ligases (CRLs ...
Alexandra Ribarits   +12 more
core   +1 more source

β‐Adrenergic Signaling Promotes Anti‐Tumor Immunity in TP53‐mutant Oral Squamous Cell Carcinoma

open access: yesAdvanced Science, EarlyView.
β‐adrenergic stimulation enhances anti‐tumor immunity in TP53‐deficient oral squamous cell carcinoma by inducing tumor‐derived secretion of CXCL10, which attracts and activates cytotoxic CD8+ T cells. The findings demonstrate that β‐adrenergic signaling alters tumor–immune interactions via CXCL10‐mediated paracrine activation, revealing a neuro‐immune ...
Frederico O. Gleber‐Netto   +20 more
wiley   +1 more source

Macrophage TRIM21 Inhibition Ameliorates Murine Acute Pancreatitis via PHB2‐Mediated Mitochondrial Stabilization

open access: yesAdvanced Science, EarlyView.
Macrophage‐derived TRIM21 drives the progression of AP via ubiquitin‐proteasome‐mediated degradation of PHB2, leading to impaired PHB2‐mediated mitophagy. Therefore, accumulation of cytosolic mtDNA hyperactivates the cGAS‐STING signaling axis, thereby amplifying inflammatory cascades.
Yansong Xu   +7 more
wiley   +1 more source

Antagonistic Ubiquitin Switching by USP7 and RNF40 Orchestrates KDM6A Homeostasis to License Coronavirus Susceptibility

open access: yesAdvanced Science, EarlyView.
We identify an antagonistic ubiquitin circuit that controls cellular permissiveness to multiple coronaviruses. The deubiquitinase USP7 stabilizes the epigenetic regulator KDM6A to upregulate viral receptors, while the E3 ligase RNF40 degrades KDM6A by catalyzing K6/K11‐ubiquitin chains of KDM6A for autophagic degradation.
Meng‐Zhuo Huang   +9 more
wiley   +1 more source

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