A5060802168- Nuclear Structure and Function
- RNA Research and Splicing
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Genomics and Chromatin Dynamics
- RNA regulation and disease
- RNA modifications and cancer
- DNA Repair Mechanisms
- Mitochondrial Function and Pathology
- Cancer-related Molecular Pathways
- CRISPR and Genetic Engineering
- Invertebrate Immune Response Mechanisms
- Amyotrophic Lateral Sclerosis Research
- Insect symbiosis and bacterial influences
- Neurogenetic and Muscular Disorders Research
- Epigenetics and DNA Methylation
- Protein Degradation and Inhibitors
- Genetics, Aging, and Longevity in Model Organisms
- NF-κB Signaling Pathways
- Advanced biosensing and bioanalysis techniques
- Melanoma and MAPK Pathways
- Medicinal Plant Pharmacodynamics Research
- Biotin and Related Studies
- Circular RNAs in diseases
- Virus-based gene therapy research
National Institutes of Health
2019-2025
Health and Human Development (2HD) Research Network
2025
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2019-2025
University of South Carolina Upstate
2023
Institute of Cytology
2009-2018
St. Petersburg State Technological Institute
2013-2018
St Petersburg University
2010
Abstract Nuclear pore complexes (NPCs) are important for cellular functions beyond nucleocytoplasmic trafficking, including genome organization and gene expression. This multi-faceted nature the slow turnover of NPC components complicates investigations how individual nucleoporins act in these diverse processes. To address this question, we apply an A uxin- I nduced D egron (AID) system to distinguish roles basket NUP153, NUP50 TPR. Acute depletion TPR causes rapid pronounced changes...
Nuclear clearance of the RNA-binding protein TDP-43 is a hallmark neurodegeneration and an important therapeutic target. Our current understanding nucleocytoplasmic transport does not fully explain its predominantly nuclear localization or mislocalization in disease. Here, we show that exits nuclei by passive diffusion, independent facilitated mRNA export. RNA polymerase II blockade RNase treatment induce efflux, suggesting RNAs sequester limit availability for Induction efflux short,...
The tumour suppressor p53 is a crucial regulator of cell cycle arrest and apoptosis by acting as transcription factor to regulate variety genes. At least in part, this control exerted via regulating expression numerous microRNAs. We identified two abundantly expressed microRNAs, miR-16 miR-26a, whose regulated during the checkpoint induced genotoxic drug, doxorubicin. Importantly, among targets these miRs are critical kinases, Chk1 Wee1. p53-dependent augmentation miR-26a levels led cells...
Abstract Nuclear export of influenza A virus (IAV) mRNAs occurs through the nuclear pore complex (NPC). Using Auxin-Induced Degron (AID) system to rapidly degrade proteins, we show that among nucleoporins localized at nucleoplasmic side NPC, TPR is key nucleoporin required for mRNAs. recruits TR anscription and EX port (TREX)−2 NPC exporting a subset cellular By degrading components TREX-2 (GANP, Germinal-center Associated Protein; PCID2, PCI domain containing 2), require replication....
Genotoxic stress inflicted by anti-cancer drugs causes DNA breaks and genome instability. double strand induced irradiation or pharmacological inhibition of Topoisomerase II activate ATM (ataxia-telangiectasia-mutated) kinase signalling pathway that in turn triggers cell cycle arrest repair. ATM-dependent gamma-phosphorylation histone H2Ax other modifications, including ubiquitnylation, promote exchange histones recruitment damage response (DDR) repair proteins. Signal transduction pathways,...
Significance The nuclear pore complex (NPC) consisting of hundreds proteins embeds into the envelope and functions as a selectively permeable barrier regulating bidirectional trafficking macromolecules between nucleoplasm cytoplasm in eukaryotic cells. However, exact copy number specific function each composite protein within NPC remain vague. To interrogate this gap knowledge, paper, we utilized high-speed single-molecule microscopy conjunction with highly auxin-inducible degron strategies...
Either inhibiting or stabilizing SUMOylation in mitosis causes defects chromosome segregation, suggesting that dynamic mitotic of proteins is critical to maintain integrity the genome. Polo-like kinase 1-interacting checkpoint helicase (PICH), a chromatin remodeling enzyme, interacts with SUMOylated chromosomal via three SUMO-interacting motifs (SIMs) control their association chromosomes. Using cell lines conditional PICH depletion/PICH replacement, we revealed associated compromised...
The nuclear lamins are extremely long-lived proteins in most cell types. As a consequence, lamin function cannot be effectively dissected with temporal precision using standard knock-down approaches. Here, we apply the auxin inducible degron (AID) system to rapidly deplete each isoform within one cycle and reveal immediate impacts of loss on nucleus. Surprisingly, neither acute A/C (LA/C), B1 (LB1), nor B2 (LB2) depletion altered shape or induced blebbing, indicating that is not sufficient...
ACTN4 is an actin-binding protein that participates in cytoskeleton organisation. It resides both the cytoplasm and nucleus physically associates with various transcription factors. Here, we describe effect of expression on transcriptional activity RelA/p65 subunit NF-kB. We demonstrate enhances RelA/p65-dependant c-fos, MMP-3 MMP-1 genes, but it does not affect TNC, ICAM1 FN1 expression. Importantly, domains are critical for nuclear translocation co-activation RelA/p65- dependent...
A series of isatin Schiff base derivatives were identified during in silico screening the small molecule library for novel activators p53. The compounds selected based on molecular docking results further validated by a high-content assay using U2OS human osteosarcoma cells with an integrated EGFP-expressing p53-dependent reporter. hit activated and stabilized p53, as shown Western blotting, at higher rates than well-known positive control Nutlin-3. Thus, p53-activating this approach...
// Serena Giovinazzi 1,2 , Pietro Sirleto 3 Vasilisa Aksenova 4 Viacheslav M. Morozov Roberto Zori 5 William C. Reinhold 6 and Alexander Ishov 1 Department of Anatomy Cell Biology, University Florida College Medicine, Gainesville, FL 2 Health Cancer Center, Bambino Gesu' Children's Hospital, Rome, Italy Molecular Pharmacology laboratory, Institute Technology Cytology, St-Petersburg, Russia Pediatrics, Genomics Bioinformatics Group, Laboratory Pharmacology, National Institute, Institutes...
One of the hallmarks cancer is c hromosome in stability (CIN), which leads to aneuploidy, translocations, and other chromosome aberrations. However, vast majority human tumors molecular basis CIN remains unknown, partly because not all genes controlling transmission have yet been identified. To address this question, we developed an experimental high-throughput imaging (HTI) siRNA assay that allows identification novel genes. Our method uses a artificial (HAC) expressing GFP transgene. When...
The Ran GTPase plays critical roles in multiple cellular processes including interphase nucleocytoplasmic transport and mitotic spindle assembly. During mitosis mammalian cells, GTP-bound (Ran-GTP) is concentrated near chromatin while GDP-bound (Ran-GDP) more abundant distal to chromosomes. This pattern spatially controls formation because Ran-GTP locally releases assembly factors (SAFs), such as Hepatoma Up-Regulated Protein (HURP), from inhibitory interactions Regulator of Chromatin...
Polo-like kinase-interacting checkpoint helicase (PICH) interacts with SUMOylated proteins to mediate proper chromosome segregation during mitosis. The results demonstrate that PICH controls the association of proteins, including topoisomerase IIa, chromosomes, requiring translocase activity and SUMO-binding ability.
Macromolecular transport between the nucleus and cytoplasm is mediated through Nuclear Pore Complexes (NPCs), which are built from multiple copies of roughly 34 distinct proteins, called nucleoporins 1–3 . Models NPC depict it as a composite several sub-domains that have been named outer rings, inner ring, cytoplasmic fibrils nuclear basket. While has extensively studied, roles individual within NPCs their functional interactions remain poorly understood. Here, we applied rapid degron system...
Abstract Identity-specific interphase chromosome conformation must be re-established each time a cell divides. To understand how folding is inherited, we developed an experimental approach that physically segregates mediators of G1 are intrinsic to mitotic chromosomes from cytoplasmic factors. Proteins essential for nuclear transport, RanGAP1 and Nup93, were degraded in pro-metaphase arrested DLD-1 cells prevent the establishment nucleo-cytoplasmic transport during exit isolate decondensing...
The maintenance of the intestinal epithelium is ensured by controlled proliferation stem cells (ISCs) and differentiation their progeny into various cell types, including enterocytes (ECs) that both mediate nutrient absorption provide a barrier against pathogens. signals regulate transition proliferative ISCs differentiated ECs are not fully understood. IRBIT an evolutionarily conserved protein regulates ribonucleotide reductase (RNR), enzyme critical for generation DNA precursors. Here, we...
Nuclear speckles are non–membrane-bound organelles known as storage sites for messenger RNA (mRNA) processing and splicing factors. More recently, nuclear have also been implicated in export of a subset mRNAs, including the influenza virus M mRNA that encodes proteins required viral entry, trafficking, budding. However, little is about how assembled or regulated. Here, we uncovered role cellular protein kinase TAO2 constituent factor integrity these bodies their functions pre-mRNA...
Selective defects in protein targeting to the nuclear envelope when nucleoporin Nup153 is depleted reveal new information about assembly.
Abstract Nuclear pore complexes (NPCs) are important for many processes beyond nucleocytoplasmic trafficking, including protein modification, chromatin remodeling, transcription, mRNA processing and export. The multi-faceted nature of NPCs the slow turnover their components has made it difficult to understand role basket nucleoporins (Nup153, Nup50 Tpr) in these diverse processes. To address this question, we used an A uxin- I nduced D egron (AID) system distinguish roles nucleoporins: Loss...