Results 171 to 180 of about 14,545 (212)

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

Restriction of Individual Branched‐Chain Amino Acids has Distinct Effects on the Development and Progression of Alzheimer's Disease in 3xTg Mice

open access: yesAdvanced Science, EarlyView.
Protein restriction (PR) slows Alzheimer's disease (AD) in mice, and other benefits of PR are due to decreased branched‐chain amino acids (BCAAs). We show that restricting any BCAA has benefits, with sex‐ and BCAA‐specific impacts on pathology, molecular signaling, and cognition.
Reji Babygirija   +22 more
wiley   +1 more source

Phase Separation of NFIB Suppresses SLC3A2‐Mediated Ferroptosis in Castration‐Resistant Prostate Cancer

open access: yesAdvanced Science, EarlyView.
Castration‐resistant prostate cancer (CRPC) remains sensitive to ferroptosis, but its intrinsic resistance is poorly understood. Here, we identify NFIB as a master suppressor. SIRT7‐mediated NFIB acetylation drives its liquid–liquid phase separation, which promotes SLC3A2 transcription to inhibit ferroptosis.
Qiunuo Li   +11 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

Real‐Time Visualization of Isoform‐Specific RAF‐KRAS Interactions in Living Cells Using FRET‐BRET Hybrid Biosensors

open access: yesAdvanced Science, EarlyView.
Hybrid FRET–BRET biosensors were developed to monitor RAF–KRAS interactions in living cells. These sensors enable real‐time visualization of interaction dynamics, quantitative spectral analysis, and validation of mutation‐selective inhibitors, providing a versatile platform for probing KRAS regulation and therapeutic responses. ABSTRACT The RAS–RAF–MEK–
Jeong‐Min Go   +12 more
wiley   +1 more source

Lipid‐Facilitated Opening of the ADAM10 Sheddase Revealed by Enhanced Sampling Simulations

open access: yesAdvanced Science, EarlyView.
Phosphatidylserine acts as a lipid trigger to enhance activation of the sheddase ADAM10. By integrating fluorescence spectroscopy assays with enhanced sampling molecular dynamics simulations, this study shows that phosphatidylserine promotes ADAM10 catalytic activity along with expansion of its extracellular domains, enhancing accessibility to scaffold
Adrien Schahl   +7 more
wiley   +1 more source

SR‐B1‐Mediated Transplacental Transfer of Hydrophobic Toxicants Disrupts Fetal Development During Barriergenesis

open access: yesAdvanced Science, EarlyView.
This study maps the spatiotemporal distribution of hydrophobic toxicants and endogenous metabolites in the developing placenta and fetus. By integrating mass spectrometry imaging with snRNA‐seq, we identify SR‐B1 as a key transporter driving early‐gestation xenobiotic transfer and reveal a critical exposure window associated with persistent fetal ...
Yixuan Huang   +10 more
wiley   +1 more source

A Testis‐Specific Aralkylamine N‐Acetyltransferase Regulates Dimorphic Sperm Function and Male Fertility in Moths

open access: yesAdvanced Science, EarlyView.
We identify a Lepidoptera‐conserved testis‐specific arylalkylamine N‐acetyltransferase (LTNAT) that governs male moth fertility via a novel mechanism. LTNAT loss disrupts eupyrene sperm mitochondrial derivatives and impairs apyrene sperm motility, offering a safe molecular target for innovative pesticides and genetic pest control.
Hao Sun   +5 more
wiley   +1 more source

Single‐Cell Transcriptomics Reveals FLS2‐Dependent Hypoxia Signaling and ERF13‐Mediated Transcription During flg22‐Triggered Immunity

open access: yesAdvanced Science, EarlyView.
This study employs sc‐RNA sequencing, genetics, and phenotyping to systematically map the cell‐type‐specific immune responses triggered by flg22. It reveals FLS2‐dependent transcriptional reprogramming in epidermal and mesophyll cells, and uncovers crosstalk between immune and hypoxia signaling pathways.
Yaping Zhou   +17 more
wiley   +1 more source

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