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"Nuclear Transport"

Lihong Yao, Shuyu Chen, Haixiong Tang, Peikai Huang, Shushan Wei, Zhenyu Liang, Ailin Tao, Qingling Zhang, Rongchang Chen
Disruption of epithelial cell-cell junctions is essential for the initiation and perpetuation of airway inflammation in asthma. We've previously reported compromised epithelial barrier integrity in a toluene diisocyanate (TDI)-induced occupational asthma model. This study is aimed to explore the role of transient receptor potential vanilloid 4 (TRPV4) and transient receptor potential ankyrin 1 (TRPA1) in the dysfunction of adherens junctions in TDI-induced asthma. Mice were sensitized and challenged with TDI for a chemical-induced asthma model...
December 4, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
Birthe Fahrenkrog, Amnon Harel
Neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Huntington's disease (HD), are characterized by intracellular aggregation of proteins. In the case of ALS and FTD, these protein aggregates are found in the cytoplasm of affected neurons and contain certain RNA-binding proteins (RBPs), namely the TAR DNA-binding protein of 43 kDa (TDP-43) and the fused in sarcoma (FUS) gene product. TDP-43 and FUS are nuclear proteins and their displacement to the cytoplasm is thought to be adverse in at least two ways: loss-of-function in the nucleus and gain-of-toxicity in the cytoplasm...
November 26, 2018: Cells
Andrzej S Tarnawski, Amrita Ahluwalia
In this editorial we comment on the article by Fukushi K et al published in the recent issue of the World Journal of Gastroenterology 2018; 24(34): 3908-3918. We focus specifically on the mechanisms of the anti-thrombotic action of aspirin, gastric mucosal injury and aging-related increased susceptibility of gastric mucosa to injury. Aspirin is widely used not only for the management of acute and chronic pain and arthritis, but also importantly for the primary and secondary prevention of cardiovascular events such as myocardial infarcts and strokes...
November 14, 2018: World Journal of Gastroenterology: WJG
Piau Siong Tan, Edward A Lemke
Phenylalanine-glycine-rich nucleoporins (FG-Nups) are intrinsically disordered proteins, constituting the selective barrier of the nuclear pore complex. They are highly dynamic under physiological conditions and studying their interaction with nuclear transport receptors (NTRs) is key to understanding the molecular mechanism of nucleocytoplasmic transport. Distinct conformational features of FG-Nups interacting with diverse NTRs can be detected by multiparameter single-molecule fluorescence energy transfer (smFRET), which is a powerful technique for studying the dynamics and interactions of biomolecules in solution...
2018: Methods in Enzymology
Friederike K Kosyna, Reinhard Depping
Nuclear transport receptors of the karyopherin superfamily of proteins transport macromolecules from one compartment to the other and are critical for both cell physiology and pathophysiology. The nuclear transport machinery is tightly regulated and essential to a number of key cellular processes since the spatiotemporally expression of many proteins and the nuclear transporters themselves is crucial for cellular activities. Dysregulation of the nuclear transport machinery results in localization shifts of specific cargo proteins and associates with the pathogenesis of disease states such as cancer, inflammation, viral illness and neurodegenerative diseases...
November 21, 2018: Cells
George J Stanley, Ariberto Fassati, Bart W Hoogenboom
The nuclear pore complex (NPC) is a proteinaceous assembly that regulates macromolecular transport into and out of the nucleus. Although the structure of its scaffold is being revealed in increasing detail, its transport functionality depends upon an assembly of intrinsically disordered proteins (called FG-Nups) anchored inside the pore's central channel, which have hitherto eluded structural characterization. Here, using high-resolution atomic force microscopy, we provide a structural and nanomechanical analysis of individual NPCs...
August 2018: Life science alliance
Chao Chen, Raffaella De Masi, Ruth Lintermann, Lennart Wirthmueller
Proteins of the Poly(ADP-Ribose) Polymerase (PARP) family modify target proteins by covalent attachment of ADP-ribose moieties onto amino acid side chains. In Arabidopsis , PARP proteins contribute to repair of DNA lesions and modulate plant responses to various abiotic and biotic stressors. Arabidopsis PARP1 and PARP2 are nuclear proteins and given that their molecular weights exceed the diffusion limit of nuclear pore complexes, an active import mechanism into the nucleus is likely. Here we use confocal microscopy of fluorescent protein-tagged Arabidopsis PARP2 and PARP2 deletion constructs in combination with site-directed mutagenesis to identify a nuclear localization sequence in PARP2 that is required for nuclear import...
2018: Frontiers in Plant Science
Joshua B Kelley, Bryce M Paschal
The sequestration of DNA within the membrane-bound nucleus is a defining characteristic of eukaryotic cells. Replication and transcription are therefore restricted to the nucleus, however, the regulation of these events relies on cytoplasmic processes including protein synthesis and signal transduction pathways. Because a variety of cellular activities depend on nuclear transport, researchers from diverse fields have found it useful to examine the nuclear localization of proteins of interest. Here we present some important technical considerations for studying nuclear and cytoplasmic localization, and provide guidance for quantifying protein levels using fluorescence microscopy and ImageJ software...
November 9, 2018: Methods: a Companion to Methods in Enzymology
Kathleen E Pieper, Robert L Unckless, Kelly A Dyer
Selfish genetic elements that manipulate gametogenesis to achieve a transmission advantage are known as meiotic drivers. Sex-ratio X-chromosomes (SR) are meiotic drivers that prevent the maturation of Y-bearing sperm in male carriers to result in the production of mainly female progeny. The spread of an SR chromosome can affect host genetic diversity and genome evolution, and can even cause host extinction if it reaches sufficiently high prevalence. Meiotic drivers have evolved independently many times, though only in a few cases is the underlying genetic mechanism known...
November 9, 2018: Molecular Ecology
Chetasi Talati, Kendra L Sweet
Selective inhibitors of nuclear export (SINE) are emerging as a potentially efficacious therapeutic strategy for overcoming resistance to conventional chemotherapy for acute myeloid leukemia. SINE specifically block the protein Exportin 1, also known as chromosomal region maintenance 1, leading to nuclear retention of cargo proteins, including several tumor suppressor proteins. Selinexor, a first generation SINE, is currently in early phase clinical studies in various combinations with promising antileukemic and pro-apoptotic activity...
October 2018: International Journal of Hematologic Oncology
Maria Sokolova, Henna M Moore, Bina Prajapati, Joseph Dopie, Leena Meriläinen, Mikko Honkanen, Rita Cerejeira Matos, Minna Poukkula, Ville Hietakangas, Maria K Vartiainen
Actin has been linked to processes spanning the whole gene expression cascade, from regulating specific transcription factors, such as myocardin-related transcription factor, to chromatin remodeling and RNA polymerase function. However, whether actin controls the transcription of only specific genes or has a global role in gene expression has remained elusive. Our genome-wide analysis reveals, for the first time, that actin interacts with essentially all transcribed genes in Drosophila ovaries. Actin co-occupies the majority of gene promoters together with Pol II, and on highly expressed genes, these two proteins also associate with gene bodies...
October 15, 2018: iScience
Sarat C Vatsavayai, Alissa L Nana, Jennifer S Yokoyama, William W Seeley
What are the most important and treatable pathogenic mechanisms in C9orf72-FTD/ALS? Model-based efforts to address this question are forging ahead at a blistering pace, often with conflicting results. But what does the human neuropathological literature reveal? Here, we provide a critical review of the human studies to date, seeking to highlight key gaps or uncertainties in our knowledge. First, we engage the C9orf72-specific mechanisms, including C9orf72 haploinsufficiency, repeat RNA foci, and dipeptide repeat protein inclusions...
October 27, 2018: Acta Neuropathologica
Subbulakshmi Suresh, Sarine Markossian, Aysha H Osmani, Stephen A Osmani
The nuclear pore complex (NPC) protein Nup2 plays interphase nuclear transport roles and in Aspergillus nidulans also functions to bridge NPCs at mitotic chromatin for their faithful co-inheritance to daughter G1 nuclei. In this study, we investigate further the interphase functions of Nup2 in A. nidulans. Although Nup2 is not required for nuclear import of all nuclear proteins after mitosis, it is required for normal G1 nuclear accumulation of the NPC nuclear basket associated components Mad2 and Mlp1 as well as the THO complex protein Tho2...
October 24, 2018: Molecular Biology of the Cell
Yibin Wu, Guojiu Fang, Xin Wang, Huipeng Wang, Wenjie Chen, Liang Li, Tao Ye, Lifeng Gong, Chongwei Ke, Yuankun Cai
BACKGROUND: Nucleoporin NUP153 (NUP153) is well known to be involved in the regulating of nuclear transport. Although NUP153 is associated with several cancers, its role in colorectal cancer (CRC) and the underlying mechanism are still unknown. OBJECTIVE: The aim of this study was to access the effect of NUP153 on the prognosis of patients with CRC, and cancer cell proliferation. METHODS: The expression levels of NUP153 in CRC tissues and matched normal colon tissues were examined by real-time quantitative PCR and immunohistochemistry...
October 9, 2018: Cancer Biomarkers: Section A of Disease Markers
Xingxing Mo, Xiao Wang, Qinmin Ge, Fan Bian
Oxidative stress is one of the key mechanisms of sepsis related organ dysfunction including stress hyperglycemia. Silent mating type information regulation 2 homolog 1 (SIRT1) could regulate glucose metabolism through its deacetylase activity. In this study, we aimed to investigate the role of SIRT1/forkhead box protein 1 (FoxO1) pathway on lipopolysaccharide (LPS) induced INS-1 cells dysfunction from aspects of oxidative stress and apoptosis. After being treated with 1 mg/L LPS together with or without SIRT1 activator resveratrol (RSV) or SIRT1 inhibitor EX527, cell viability, ROS generation, malondialdehyde (MDA), superoxide, insulin secretion, and activity of superoxide dismutase (SOD) in INS-1 cells were measured by specific assays...
October 20, 2018: Stress: the International Journal on the Biology of Stress
Qianhao Xu, Tianyuan Zhang, Qiyue Wang, Xinchi Jiang, Ai Li, Ying Li, Ting Huang, Fangyuan Li, Ying Hu, Daishun Ling, Jianqing Gao
Recent advances in nanomaterials have made iron oxide nanoparticles (IONPs) as an innovative approach for the delivery of genes. However, the effectiveness of IONPs-assisted gene delivery is currently suffering from their poor uniformity, which not only exhibits detrimental effect on the magnetic property, but also leads to the poor reproducibility to maintain the optimal gene delivery. To this end, the present study developed extremely uniform 15 nm-sized IONPs with a good monodispersity in water phase. These ultra-uniform IONPs exhibit notable potentials for an efficient gene delivery to human mesenchymal stem cells (hMSCs) with the assistance of magnetic force, which partly owes to their abilities to facilitate the cellular uptake, as well as to induce the rapid DNA release and the following nuclear transport...
December 1, 2018: International Journal of Pharmaceutics
Vasco Koch, Marianne Otte, Martin Beye
Short linear motifs (SLiMs) can play pivotal functional roles in proteins, such as targeting proteins to specific subcellular localizations, modulating the efficiency of translation and tagging proteins for degradation. Until recently we had little knowledge about SLiM evolution. Only a few amino acids in these motifs are functionally important, making them likely to evolve ex nihilo and suggesting that they can play key roles in protein evolution. Several reports now suggest that these motifs can appear and disappear while their function in the protein is preserved, a process sometimes referred to as "turnover"...
October 4, 2018: G3: Genes—Genomes—Genetics
Jun Li, Yuan Zhou, Yang Liu, Bo Dai, Yu-Hen Zhang, Peng-Fei Zhang, Xiao-Lei Shi
Sorafenib has been demonstrated to be a beneficial treatment for advanced hepatocellular carcinoma (HCC). Emerging evidence indicates that caspase-1 activation plays a crucial role in HCC progression. However, the relationship between caspase-1 and sorafenib has rarely been reported. In this study, we showed that caspase-1 was essential for lipopolysaccharide (LPS)-induced epithelial-mesenchymal transition (EMT). Moreover, sorafenib treatment could inhibit LPS-stimulated caspase-1 overexpression through restricting the nuclear transport of p65, which contributed to inactivation of NF-κB...
October 2, 2018: Cancer Biology & Therapy
Changjie Lv, Wenkai Liu, Bin Wang, Ruyi Dang, Li Qiu, Juan Ren, Chuanqi Yan, Zengqi Yang, Xinglong Wang
Pseudorabies virus (PRV) is an important viral pathogen of pigs that causes huge losses in pig herds worldwide. Ivermectin is a specific inhibitor of importin-α/β-dependent nuclear transport and shows antiviral potential against several RNA viruses by blocking the nuclear localization of viral proteins. Since the replication of DNA viruses is in the nucleus, ivermectin may be functional against DNA virus infections if the DNA polymerase or other important viral proteins enter the nucleus via the importin-α/β-mediated pathway...
September 26, 2018: Antiviral Research
Qinyi Zhou, Jun Chen, Jialin Feng, Jiadong Wang
Iron homeostasis is critical to mammals, and dysregulation in iron homeostasis usually leads to severe disorders including various cancers. Massive hepcidin secretion is an indicator of thyroid cancer, but the molecular mechanisms responsible for this dysregulation are unknown. Hepcidin secretion from thyroid cancer cells also leads to decreased expression of the iron exporter, ferroportin (FPN), and increased intracellular iron retention, which promote cancer proliferation. In this study, we examined the role of hepcidin in thyroid cancer (TC) and the molecular bases of its signaling...
September 24, 2018: Cell Death & Disease
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