Diptoindonesin G (dip G) has been identified as a promising HSP90 modulator that promotes degradation of oncogenic proteins, such as the estrogen receptor, without triggering the heat shock response, offering a potential new therapy for endocrine-resistant breast cancers that harbor estrogen receptor ligand-binding domain mutations. Unlike traditional endocrine therapies, dip G's mechanism of action is unaffected by mutations that confer resistance to current treatments, suggesting it could be an effective strategy against a broader range of cancer cells, including those with established mechanisms of endocrine resistance.
In this JBC paper, the authors discovered that these endoplasmic reticulum and mitochondrial proteins moved toward each other and met at the contact site between the two organelles, thereby forming a ‘bridge to death’.
The development of new protein functionalities by incorporating non-coded amino acids into biotechnological applications requires overcoming natural barriers that prevent incorrect amino acid incorporation during protein synthesis. This rapidly evolving field benefits from the discovery and design of new tools, often inspired by archaeal biology. A recent study published in JBC examines one such tool, exploring its development and uncovering surprising aspects of how the universal genetic code machinery came to be.
Hsp90, a molecular chaperone involved in protein folding and stabilization, is targeted for drug development due to its role in diseases caused by protein misfolding, such as cancer and neurodegenerative disorders. A recent study highlights diptoindonesin G as a novel Hsp90 inhibitor that degrades the estrogen receptor, a client protein of Hsp90, without triggering the heat shock response.
They introduce a novel mass spectrometry-based proteomic method that effectively isolates and quantifies mitochondrial-encoded proteins, overcoming challenges due to their hydrophobic nature and scarcity. This technique, which uses pulse stable isotope labeling, has proven superior in protein identification rate and efficiency, allowing for the analysis of 12 out of the 13 proteins involved in oxidative phosphorylation. By applying this method, they gained insights into the (post-)translational regulation within oxidative phosphorylation complexes and observed the impact of mitochondrial translation inhibition on the stability of certain nuclear-encoded subunits.
The authors have recently clarified the complex interactions within the partitioning–defective protein system, which is crucial for establishing cell polarity in animals, by reconstituting some of these interactions in vitro, as detailed in a Journal of Biological Chemistry article. Despite the system's foundation on just four core proteins, this achievement simplifies the previously complex understanding of how these proteins organize and function at the molecular level.
This JBC paper reveals how alternative splicing of a single CaV3 gene in the pond snail (Lymnaea stagnalis) allows it to produce channels permeable to either Ca2+ or Na+, demonstrating a nuanced control over ion selectivity. This finding illuminates the evolutionary adaptability and physiological tuning of ion channels, which, despite their similar structures, achieve distinct ion selectivity through specific amino acid sequences in the selectivity filter.
This study explores how erucic acid (EA), a very long-chain fatty acid, affects Alzheimer's disease (AD) progression by altering cell membrane composition in AD model cells. EA-induced membrane remodeling leads to significant changes in the lipid environment, which enhances γ-secretase activity to produce potentially less harmful amyloid-β (Aβ) species, Aβ37 and Aβ38, across various cell lines. Interestingly, while EA remodeling increases total Aβ secretion in cells with normal γ-secretase, it decreases in cells with a familial AD-associated γ-secretase mutation. These findings suggest that modifying membrane lipids can impact Aβ production in complex ways, offering insights for lipid-based AD treatments. This highlights the potential of targeting lipid metabolism in AD therapy, considering the intricate relationship between lipid homeostasis and amyloid processing.
Hsu and colleagues have recently elucidated the inhibitory mechanism of a proteasome inhibitor that has been of interest for over three decades, utilizing cryo-electron microscopy. This breakthrough, detailed in the Journal of Biological Chemistry, not only clarifies how the inhibitor operates across multiple sites to hinder proteasomal protease activity through a combination of structural, biochemical, and cell-based experiments but also introduces intriguing new inquiries regarding proteasome subpopulations involved in the process.
The study explores the effectiveness of a deep learning AI model, trained on time-lapse images of embryos, in improving embryo selection processes in in vitro fertilization (IVF). Utilizing a dataset from 18 IVF centers encompassing over 115,000 embryos, the model demonstrated promising results by accurately scoring embryos' potential for successful implantation, showing adaptability across various patient ages and clinical conditions. It performed comparably to traditional selection methods while offering the advantages of automation, consistency, and the elimination of subjective biases.
Non-invasive detection of SARS-CoV-2 infection by canine olfaction could be one alternative to NPS RT-PCR when it is necessary to obtain a result very quickly according to the same indications as antigenic tests in the context of mass screening.
Great article! This technique identified distinct clusters of embryonic nuclei with specific gene expression patterns that correspond to spatial regions within the embryo, and provided a list of genes showing local expression differences in embryos lacking the insulator protein dCTCF, underscoring its potential to uncover novel insights into embryonic gene regulation.
Recent scientific analysis of coins attributed to the enigmatic Roman emperor Sponsian, once thought to be forgeries due to their unorthodox design and manufacture, suggests their authenticity based on wear patterns and signs of long-term burial. This evidence, combined with historical context, supports the theory that Sponsian was a military commander in Dacia during the 260s CE, whose locally produced coins played a key role in the region's economy amidst a period of crisis.
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