The nucleocytoplasmic translocation of HINT1 regulates the maturation of cell density

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

Опубликована: Янв. 14, 2025

Abstract Cell contact inhibition progresses through three stages: (i) increasing cell density leads to reduced movement while mitosis continues; (ii) a rapid shift epithelial morphology; and (iii) ongoing division with decreased size. This transition involves reorganizing the actin cytoskeleton from stress fibers cortical network, stabilizing shape, strengthening cell-cell connections. However, signaling pathways regulating final stage remain unclear. We identified histidine triad nucleotide-binding protein 1 (HINT1), also known as kinase C inhibitor (PKCI-1), essential for monolayer maturation. At low density, HINT1 is located in nucleus, binding open chromatin. As increases, exportin-1 relocates cytoplasm, where it inhibits PKC remodels cytoskeleton. While formation can occur without HINT1, its presence necessary fully confining cells achieving mature monolayer. Additionally, MARCKS phosphorylation decreases high-density cells, loss of increased area, similar hypertrophic conditions patients levels. Summary blurb Histidine shuttles between nucleus cytoplasm based on gene expression inhibiting remodel actin.

Язык: Английский

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Modulation of Gene Expression by Substrate Stiffness via Ubiquitination of Histone H2B by Ubiquitin-Conjugating Enzyme E2A/B

ACS Omega, Год журнала: 2025, Номер unknown

Опубликована: Апрель 9, 2025

Язык: Английский

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The WAVE complex forms linear arrays at negative membrane curvature to instruct lamellipodia formation.

Опубликована: Июль 8, 2024

Cells generate a wide range of actin-based membrane protrusions for various cell behaviors. These are organized by different actin nucleation promoting factors. For example, N-WASP controls finger-like filopodia, whereas the WAVE complex sheet-like lamellipodia. morphologies likely reflect patterns nucleator self-organization. phase separation has been successfully studied through biochemical reconstitutions, but how self-organizes to instruct lamellipodia is unknown. Because self-organization proven refractory cell-free studies, we leverage in vivo approaches investigate organization within its native cellular context. With single molecule tracking and molecular counting, show that forms highly regular multi-layered linear arrays at plasma rem-iniscent microtubule-like organization. Similar microtubule protofilaments curved array, curvature both necessary sufficient formation these arrays, though polymerization not. This dependency on negative could explain templating their emergent behaviors, including barrier avoidance. Our data uncover key biophysical properties mesoscale patterning highlight an integral relationship between NPF morphogenesis.

Язык: Английский

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Role of Filamin A in Growth and Migration of Breast Cancer—Review

Current Issues in Molecular Biology, Год журнала: 2024, Номер 46(4), С. 3408 - 3423

Опубликована: Апрель 17, 2024

Despite ongoing research in the field of breast cancer, morbidity rates indicate that disease remains a significant challenge. While patients with primary tumors have relatively high survival rates, these chances significantly decrease once metastasis begins. Thus, exploring alternative approaches, such as targeting proteins overexpressed malignancies, significant. Filamin A (FLNa), an actin-binding protein (ABP), is involved various cellular processes, including cell migration, adhesion, proliferation, and DNA repair. Overexpression was confirmed samples from numerous oncological diseases prostate, lung, gastric, colorectal, pancreatic well cancer. Although most researchers concur on its role promoting cancer progression aggressiveness, discrepancies exist among studies. Moreover, precise mechanisms through which FLNa affects invasion, even remain unclear, highlighting need for further research. To evaluate FLNa’s potential therapeutic target, we summarized roles

Язык: Английский

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Characterization of open chromatin sensitive to actin polymerization and identification of core‐binding factor subunit beta as mechanosensitive nucleocytoplasmic shuttling protein

Cytoskeleton, Год журнала: 2024, Номер unknown

Опубликована: Сен. 6, 2024

Abstract Mechanotransduction leads to a variety of biological responses including gene expression, changes in cell shape, migration, tissue development, and immune responses. Dysregulation mechanotransduction is implicated the progression various diseases such as cardiovascular cancer. The actin cytoskeleton plays crucial role transmitting mechanical stimuli. Actin filaments, essential for motility shape changes, respond cues by remodeling, influencing expression via linker nucleoskeleton complex mechanosensitive transcription factors. This study employs dithiobis(succinimidyl propionate) (DSP)‐micrococcal nuclease (MNase) proteogenomics method explore relationship between cellular mechanosensing, chromatin architecture, identification proteins involved nucleocytoplasmic shuttling, revealing how polymerization affects expression. We found that depolymerization filaments latrunculin B (Lat B) 30 min sufficient alter open identified core‐binding factor subunit beta shuttling protein.

Язык: Английский

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Intermediate filaments and their associated molecules

Journal of Biomedical Research, Год журнала: 2024, Номер 38, С. 1 - 1

Опубликована: Янв. 1, 2024

Intermediate filaments (IFs) in human cells are the products of six distinct gene families, all sharing homology a core rod domain. These IFs assemble into non-polar polymers, providing cytoplasmic and nuclear mechanical support. Recent research has revealed active dynamic properties their binding partners. This regulation extends beyond cell mechanics to include migration, mechanotransduction, tumor growth. comprehensive review will catalog IF genes IF-associated proteins (IFAPs), detailing names, sizes, functions, associated diseases, relevant literature, links resources like Uniprot Protein Atlas database. provide access additional information such as protein structure, subcellular localization, disease-causing mutations, pathology. Using this catalog, we overview current understanding biological functions IFAPs. is crucial for identifying gaps characterization IF-mediated mechanotransduction. Additionally, consider potential future directions.

Язык: Английский

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Comparative transcriptomic analysis validates iPSC derived in-vitro progressive fibrosis model as a screening tool for drug discovery and development in systemic sclerosis

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Окт. 18, 2024

Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, immune dysregulation, and systemic fibrosis. Research on SSc has been hindered largely lack of relevant models to study the progressive nature recapitulate cell plasticity that observed in this context. Generation for fibrotic using pluripotent stem cells important recapitulating heterogeneity tissue are a potential platform screening anti-fibrotic drugs. We previously reported novel in-vitro model fibrosis induced cell-derived mesenchymal (iSCAR). Here we report generation "scar-like phenotype" when iPSC derived cultured hydrogel mimicks wound healing/scarring response First, performed RNA sequencing (RNA-seq) based transcriptome profiling iSCAR culture at 48 h 13 days characterize early latestage scarring phenotypes. The next RNA-seq these different timepoints detected expression 92% "scar associated" genes 85% late genes, respectively. Comparative transcriptomic analysis gene level compendium matrix associated revealed common both data sets. Early scar formation showed biological processes hypoxia (27.5%), vascular development (13.7%) glycolysis (27.5), while with senescence (22.6%). Next show effects two antifibrotic compounds validate utility as tool late-stagelate-stage An autotaxin inhibitor was used stage (iSCAR-T) compound unknown mechanism (EX00015097) (iSCAR-P) late-stage model.

Язык: Английский

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TPM4 overexpression drives colon epithelial cell tumorigenesis by suppressing differentiation and promoting proliferation

Neoplasia, Год журнала: 2024, Номер 59, С. 101093 - 101093

Опубликована: Ноя. 28, 2024

Язык: Английский

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