Behind the stoNE wall: a fervent activity for nuclear lipids

Biochimie, Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

Язык: Английский

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Genome concentration limits cell growth and modulates proteome composition in Escherichia coli

eLife, Год журнала: 2024, Номер 13

Опубликована: Май 10, 2024

Defining the cellular factors that drive growth rate and proteome composition is essential for understanding manipulating systems. In bacteria, ribosome concentration known to be a constraining factor of cell rate, while gene usually assumed not limiting. Here, using single-molecule tracking, quantitative single-cell microscopy, modeling, we show genome dilution in Escherichia coli cells arrested DNA replication limits total RNA polymerase activity within physiological sizes across tested nutrient conditions. This rapid-onset limitation on bulk transcription results sub-linear scaling active ribosomes with size sub-exponential growth. Such downstream effects translation are near-immediately detectable nutrient-rich medium, but delayed nutrient-poor conditions, presumably due buffering activities. sequencing tandem-mass-tag mass spectrometry experiments further reveal remodels relative abundance mRNAs proteins at global level. Altogether, our findings indicate chromosome limiting modulator transcriptome E. . Experiments Caulobacter crescentus comparison eukaryotic studies identify broadly conserved concentration-dependent principles expression.

Язык: Английский

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An unscheduled switch to endocycles induces a reversible senescent arrest that impairs growth of the Drosophila wing disc

PLoS Genetics, Год журнала: 2024, Номер 20(9), С. e1011387 - e1011387

Опубликована: Сен. 3, 2024

A programmed developmental switch to G / S endocycles results in tissue growth through an increase cell size. Unscheduled, induced endocycling cells (iECs) promote wound healing but also contribute cancer. Much remains unknown, however, about how these iECs affect growth. Using the D . melanogaster wing disc as model, we find that populations of initially size then subsequently undergo a heterogenous arrest causes severe undergrowth. acquired DNA damage and activated Jun N-terminal kinase (JNK) pathway, but, unlike other stressed cells, were apoptosis-resistant not eliminated from epithelium. Instead, entered JNK-dependent reversible senescent-like arrest. Senescent promoted division diploid neighbors, this compensatory proliferation did rescue Our study has uncovered unique attributes their effects on have important implications for understanding roles

Язык: Английский

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Aging and tumors: a dynamic interaction

Discover Oncology, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 21, 2025

Abstract Aging is an inevitable physiological process in organisms, and the development of tumors closely associated with cellular senescence. This article initially examines role senescence tumorigenesis, emphasizing correlation between telomere length—a marker senescence—and tumor risk. Concurrently, study explores expression levels senescence-associated markers, such as p16, p53, mTOR, context development. Additionally, investigates impact on organismal senescence, including effects immune system function metabolic processes. Ultimately, discussion potential application anti-aging strategies therapy considers possibility utilizing mechanisms a novel therapeutic approach for tumors. research provides insights into complex interplay development, suggesting future preventative measures interventions.

Язык: Английский

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Didymin Inhibits Proliferation and Induces Apoptosis in Gastric Cancer Cells by Modulating the PI3K/Akt Pathway

Nutrition and Cancer, Год журнала: 2025, Номер unknown, С. 1 - 16

Опубликована: Янв. 23, 2025

Gastric cancer (GC) is a malignant tumor with high morbidity and mortality rates worldwide. This study aimed to investigate the effects mechanisms of action didymin, dietary flavonoid glycoside, on GC treatment. Human cell lines Hs-746T AGS were used assess didymin viability, proliferation, cycle. The results showed that decreased proliferative capacity cells blocked Didymin wound healing, invasion, migration capacities cells. Mitochondrial reactive oxygen species (ROS) levels mitochondrial membrane potentials reduced in treated didymin. Network pharmacology analysis revealed therapeutic related phosphatidylinositol 3-kinase (PI3K)/Akt pathway. In vivo mouse xenograft studies confirmed treatment cycle protein levels, Akt phosphorylation. present demonstrated regulates function PI3K/Akt pathway inhibit proliferation induce apoptosis vitro vivo. Therefore, promising drug for GC.

Язык: Английский

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Temporal Myc dynamics permit mitotic bypass, promoting polyploid phenotypes

Cancer Letters, Год журнала: 2025, Номер 613, С. 217526 - 217526

Опубликована: Фев. 3, 2025

Язык: Английский

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A novel RNP compartment boosts translation in growing mouse oocytes to avoid cytoplasm dilution

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Abstract Mammalian oocytes undergo a long growth phase in the ovary, during which transcriptional levels gradually decrease. Growing must therefore accumulate maternal stores and regulate their translation to achieve successful divisions early embryo development. Using immunofluorescence, mass spectrometry electron microscopy, we identified novel transient compartment, Zollo Body, late growing mouse oocytes, constituted of RNPs organelles. Morphologically, this structure resembles Balbiani body found most vertebrate species but it stains positively for nascent active phospho-mTOR. RNAseq analysis dry measurements with or without compartment further support its key role boosting translation, allowing avoid cytoplasmic dilution despite rapid size increase, ultimately ensuring developmental potential.

Язык: Английский

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ИНФЛАМЕЙДЖИНГ: РОЛЬ СЕНЕСЦЕНТНЫХ КЛЕТОК В ПАТОГЕНЕЗЕ ОСТЕОАРТРИТА

Успехи геронтологии, Год журнала: 2025, Номер 37(6), С. 777 - 786

Опубликована: Фев. 20, 2025

Язык: Русский

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p21-Dependent Senescence Induction by BMP4 Renders Glioblastoma Cells Vulnerable to Senolytics

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(9), С. 3974 - 3974

Опубликована: Апрель 23, 2025

Glioblastoma (GBM) is a highly malignant brain tumor with extensive cellular heterogeneity and plasticity. Bone morphogenetic protein 4 (BMP4) has shown potential as therapeutic agent by promoting differentiation, but its effects are complex context dependent. While BMP4’s role in differentiation well established, impact on senescence remains unclear. This study investigates ability to induce GBM cells. Primary cultures were treated BMP4 analyzed for markers, including cell enlargement, p21 expression, senescence-related gene enrichment, senescence-associated-β-galactosidase activity. A knockout model was used determine BMP4-induced senescence, sensitivity the senolytic navitoclax evaluated. induced cultures, particularly mesenchymal (MES)-like cells high baseline levels. The of nearly abolished maintaining size proliferation. Furthermore, effectively eliminated senescent through apoptosis, while sparing normal expression. Our findings highlight an inducer p21-dependent GBM, MES-like clarifies dual roles emphasizing their dependence. Given strong link between therapy resistance, heightened susceptibility may aid developing targeted therapies potentially other cancers similar dynamics.

Язык: Английский

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Genome concentration limits cell growth and modulates proteome composition inEscherichia coli

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Фев. 29, 2024

ABSTRACT Defining the cellular factors that drive growth rate and proteome composition is essential for understanding manipulating systems. In bacteria, ribosome concentration known to be a constraining factor of cell rate, while gene usually assumed not limiting. Here, using single-molecule tracking, quantitative single-cell microscopy, modeling, we show genome dilution in Escherichia coli cells arrested DNA replication limits total RNA polymerase activity within physiological sizes across tested nutrient conditions. This rapid-onset limitation on bulk transcription results sub-linear scaling active ribosomes with size sub-exponential growth. Such downstream effects translation are near-immediately detectable nutrient-rich medium, but delayed nutrient-poor conditions, presumably due buffering activities. sequencing tandem-mass-tag mass spectrometry experiments further reveal remodels relative abundance mRNAs proteins at global level. Altogether, our findings indicate chromosome limiting modulator transcriptome E. . Experiments Caulobacter crescentus comparison eukaryotic studies identify broadly conserved concentration-dependent principles expression.

Язык: Английский

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