Results 101 to 110 of about 122,814 (265)

mTORC2 Phosphorylation of GSDME‐N Drives Cullin4B‐Mediated Proteasomal Degradation to Suppress Pyroptosis and Confer Radioresistance in Small Cell Lung Cancer

open access: yesAdvanced Science, EarlyView.
Radioresistance severely limits the efficacy of therapies for small cell lung cancer (SCLC). This study reveals a novel mechanism of resistance driven by the active suppression of pyroptosis. Specifically, the mTORC2 complex directly phosphorylates GSDME‐N and promotes its CUL4B‐mediated ubiquitination and proteasomal degradation.
Qing‐qing Xu   +11 more
wiley   +1 more source

Sertraline treatment prevents motor dysfunction in a Huntington's disease mouse model and functional decline in patients

open access: yesNeurotherapeutics
Molecular alterations underlying Huntington's disease (HD) are not fully elucidated and no curative therapies are available. We have described that increased translation efficiency participates in the motor symptoms in the R6/1 HD mouse model.
Marta Garcia-Forn   +11 more
doaj   +1 more source

Targeting KDM3B Elicits Anti‐tumor Immunity by Alleviating SHP1–mediated STING Suppression in Triple–Negative Breast Cancer

open access: yesAdvanced Science, EarlyView.
P3FI–90 treatment targets KDM3B, reshapes the epigenetic landscape, and suppresses SHP1 expression, thereby activating STING–TBK1–IRF3–type I IFN signaling pathway. Consequently, CD8+ T cells are recruited to the tumor site and activated to produce IFN–γ and GZMB, leading to the killing of TNBC cells.
Xiaolong Wang   +8 more
wiley   +1 more source

Discovery and Engineering of a Rat Endogenous Retrovirus Reverse Transcriptase for Efficient Prime Editing

open access: yesAdvanced Science, EarlyView.
We screened 558 reverse transcriptases and engineered an optimized rat endogenous retrovirus‐derived variant, enRERV‐RT, via structure‐guided engineering and deep mutational scanning. This enhanced prime editor, based on the engineered RT, outperforms conventional M‐MLV‐RT systems across plant and animal cells, particularly at hard‐to‐edit loci ...
Linsha Ma   +22 more
wiley   +1 more source

CCT2 Promotes Prostate Cancer Progression Through EIF3F‐Dependent Stabilization of FASN

open access: yesAdvanced Science, EarlyView.
ABSTRACT Prostate cancer (PCa) is increasingly recognized to be driven by dysregulated lipid metabolism. Although fatty acid synthase (FASN) is highly expressed in PCa, the mechanisms governing FASN protein stability and its functional integration into oncogenic lipid metabolism remain poorly defined.
Shun Xu   +13 more
wiley   +1 more source

PDIA6–SCD1 Axis Rewires Lipid Metabolism to Drive Gastric Cancer Progression

open access: yesAdvanced Science, EarlyView.
Protein disulfide isomerase A6 (PDIA6) is identified as an oncogenic driver in gastric cancer. PDIA6 directly binds and stabilizes SCD1 by limiting its ubiquitin–proteasome‐mediated degradation, thereby sustaining monounsaturated fatty acid (MUFA)‐enriched lipid homeostasis and lipid metabolic reprogramming.
Zhen Tian   +13 more
wiley   +1 more source

Cholesterol‐Mediated Metabolic‐mechanotransductive Crosstalk Orchestrates Castration Resistance in Prostate Cancer

open access: yesAdvanced Science, EarlyView.
Full androgen deprivation (FAD) induces paracrine cholesterol in prostate cancer that drives the polarization of cancer‐associated fibroblasts (CAFs) and subsequent elevated matrix stiffness. Matrix stiffness in turn potentiates tumor cell survival under FAD pressure via dual mechanotransductive activation of the IRE1α‐XBP1s stress‐response axis ...
Shaojie Liu   +20 more
wiley   +1 more source

RNF138‐Mediated Ubiquitination and Degradation of NS5 Restricts Tick‐Borne Encephalitis Virus Infection

open access: yesAdvanced Science, EarlyView.
Host‐specific compatibility between RNF138‐like proteins and flavivirus NS5 determines NS5 stability. Mammalian RNF138 but not arthropod homologs recognizes and induces conserved NS5/RdRp K48‐linked ubiquitination and proteasomal degradation, thereby restricting viral replication. Ectopic RNF138 in mice attenuates TBEV‐induced pathogenesis. (Created in
Jialiang Sun   +6 more
wiley   +1 more source

FOS3D: A Fluorescence‐Enabled Toolkit for Characterizing a Three‐dimensional Osteosarcoma Model

open access: yesAdvanced Science, EarlyView.
FOS3D describes fluorescent (F) osteosarcoma (OS) cells in a tri‐dimensional (3D) model. The study comprises three phases: development, where biofabrication parameters are tuned to achieve cytocompatibility and tumor‐specific mechanical properties in cell‐laden gelatin methacryloyl constructs; validation, where whole‐well fluorescence reading is ...
William Humble   +9 more
wiley   +1 more source

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