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"Nuclear Transport"

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...
October 9, 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
Asako McCloskey, Arkaitz Ibarra, Martin W Hetzer
The total number of nuclear pore complexes (NPCs) per nucleus varies greatly between different cell types and is known to change during cell differentiation and cell transformation. However, the underlying mechanisms that control how many nuclear transport channels are assembled into a given nuclear envelope remain unclear. Here, we report that depletion of the NPC basket protein Tpr, but not Nup153, dramatically increases the total NPC number in various cell types. This negative regulation of Tpr occurs via a phosphorylation cascade of extracellular signal-regulated kinase (ERK), the central kinase of the mitogen-activated protein kinase (MAPK) pathway...
October 1, 2018: Genes & Development
Kylie M Wagstaff, Stephen Headey, Sushama Telwatte, David Tyssen, Anna C Hearps, David R Thomas, Gilda Tachedjian, David A Jans
Human immunodeficiency virus (HIV) continues to be a major contributor to morbidity and mortality worldwide, particularly in developing nations where high cost and logistical issues severely limit the use of current HIV therapeutics. This, combined HIV's high propensity to develop resistance, means that new antiviral agents against novel targets are still urgently required. We previously identified novel anti-HIV agents directed against the nuclear import of the HIV integrase (IN) protein, which plays critical roles in the HIV lifecycle inside the cell nucleus, as well as in transporting the HIV preintegration complex (PIC) into the nucleus...
September 14, 2018: Cellular Microbiology
Sen Zhang, Hao Qi, Xue-Peng Wen, Ping Li, Xue-Jun Gao, Jin-Xia Ao
Tudor staphylococcal nuclease (Tudor-SN) is a multifunctional protein involved in a variety of cellular processes and plays a critical role in the regulation of gene expression. Recently, Tudor-SN was found to be upregulated in mammary epithelial cells during lactation in response to prolactin, which further to regulate milk protein synthesis. However, the detailed regulatory mechanism of Tudor-SN to milk protein still remains to be elucidated. In our study, we observed that the levels of Tudor-SN and phosphor-Tudor-SN (Thr103) were both enhanced upon prolactin stimulation...
September 6, 2018: Journal of Cellular Physiology
Yun Jung Yang, Danielle J Mai, Thomas J Dursch, Bradley D Olsen
Biological systems routinely regulate biomolecular transport with remarkable specificity, low energy input, and simple mechanisms. Here, the biophysical mechanisms of nuclear transport inspire the development of gels for recognition and selective permeation (GRASP). GRASP presents a new paradigm for specific transport and selective permeability, in which binding interactions between a biomolecule and a hydrogel lead to faster penetration of the gel. A molecular transport theory identifies key principles for selective transport: entropic repulsion of noninteracting molecules and affinity-mediated diffusion of multireceptor biomolecules through a walking mechanism...
September 5, 2018: Biomacromolecules
Markus Schneider, Aylin Yigitliler, Frank Stubenrauch, Thomas Iftner
The papillomavirus (PV) E2 protein is a nuclear, sequence-specific DNA-binding protein that regulates transcription and nuclear retention of viral genomes. E2 also interacts with the viral E1 protein to replicate the viral genome. E2 residue K111 is highly conserved among PV and has been implicated in contributing to nuclear transport, transcription and replication. Cottontail rabbit (sylvilagus floridanus) PV (CRPV or SfPV1) E2 K111R, A or Q mutations are transcription-deficient and localized to the cytoplasm comparable to other PV types...
August 22, 2018: Journal of Virology
Yichen Li, Samuel L Junod, Andrew Ruba, Joseph M Kelich, Weidong Yang
The nuclear exit of messenger RNA (mRNA) molecules through the nuclear pore complex (NPC) is an essential step in the translation process of all proteins. The current limitations of conventional fluorescence and electron microscopy have prevented elucidation of how mRNA exports through the NPCs of live cells. In the recent years, various single-molecule fluorescence (SMF) microscopy techniques have been developed to improve the temporal and spatial resolutions of live-cell imaging allowing a more comprehensive understanding of the dynamics of mRNA export through native NPCs...
August 18, 2018: Methods: a Companion to Methods in Enzymology
Claudia Abeijon, Julia Dilo, Jacqueline M Tremblay, Agostinho G Viana, Lilian L Bueno, Silvio F G Carvalho, Ricardo T Fujiwara, Charles B Shoemaker, Antonio Campos-Neto
We have recently developed a sensitive and specific urine-based antigen detection ELISA for the diagnosis of visceral leishmaniasis (VL). This assay used rabbit IgG and chicken IgY polyclonal antibodies specific for the Leishmania infantum proteins iron superoxide dismutase 1 (Li-isd1), tryparedoxin1 (Li-txn1) and nuclear transport factor 2 (Li-ntf2). However, polyclonal antibodies have limitations for upscaling and continuous supply. To circumvent these hurdles, we began to develop immortalized monoclonal antibodies...
August 18, 2018: Parasite Immunology
Veronica Rodriguez-Bravo, Raffaella Pippa, Won-Min Song, Marc Carceles-Cordon, Ana Dominguez-Andres, Naoto Fujiwara, Jungreem Woo, Anna P Koh, Adam Ertel, Ravi K Lokareddy, Alvaro Cuesta-Dominguez, Rosa S Kim, Irene Rodriguez-Fernandez, Peiyao Li, Ronald Gordon, Hadassa Hirschfield, Josep M Prats, E Premkumar Reddy, Alessandro Fatatis, Daniel P Petrylak, Leonard Gomella, W Kevin Kelly, Scott W Lowe, Karen E Knudsen, Matthew D Galsky, Gino Cingolani, Amaia Lujambio, Yujin Hoshida, Josep Domingo-Domenech
Nuclear pore complexes (NPCs) regulate nuclear-cytoplasmic transport, transcription, and genome integrity in eukaryotic cells. However, their functional roles in cancer remain poorly understood. We interrogated the evolutionary transcriptomic landscape of NPC components, nucleoporins (Nups), from primary to advanced metastatic human prostate cancer (PC). Focused loss-of-function genetic screen of top-upregulated Nups in aggressive PC models identified POM121 as a key contributor to PC aggressiveness. Mechanistically, POM121 promoted PC progression by enhancing importin-dependent nuclear transport of key oncogenic (E2F1, MYC) and PC-specific (AR-GATA2) transcription factors, uncovering a pharmacologically targetable axis that, when inhibited, decreased tumor growth, restored standard therapy efficacy, and improved survival in patient-derived pre-clinical models...
August 23, 2018: Cell
Masahiro Oka, Yoshihiro Yoneda
Nucleocytoplasmic transport is an essential process in eukaryotes. The molecular mechanisms underlying nuclear transport that involve the nuclear transport receptor, small GTPase Ran, and the nuclear pore complex are highly conserved from yeast to humans. On the other hand, it has become clear that the nuclear transport system diverged during evolution to achieve various physiological functions in multicellular eukaryotes. In this review, we first summarize the molecular mechanisms of nuclear transport and how these were elucidated...
2018: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
Vishakha Dey, Swati Patankar
Importin α is nuclear transport receptor that recognises nuclear localisation sequences (NLS). The protein has two domains: armadillo (ARM) repeats containing NLS-binding sites and the importin β-binding (IBB) domain. The IBB domain mimics an NLS and can bind to the ARM repeats, preventing NLS binding. This phenomenon, called auto-inhibition, is a key regulatory feature for binding and release of NLS-containing cargo by importin α and mutants that lack auto-inhibition show impaired viability in Saccharomyces cerevisiae...
September 10, 2018: Biochemical and Biophysical Research Communications
Xujie Liu, Wenbo Lin, Xiuyu Shi, Rebecca G Davies, Kylie M Wagstaff, Tao Tao, David A Jans
Importin 13 (IPO13) is a key member of the importin β superfamily, which can transport cargoes both into and out of the nucleus to contribute to a variety of important cellular processes. IPO13 is known to undergo phosphorylation, but the impact of this on function has not been investigated. Here, we show for the first time that IPO13 is phosphorylated by cAMP-dependent protein kinase A specifically at serine 193. Results from fluorescence recovery after photobleaching and fluorescence loss in photobleaching approaches establish that negative charge at serine 193 through phosphorylation or point mutation both reduces IPO13 nuclear import and increases its nuclear export...
August 31, 2018: Biochemical Journal
Elham Barazeghi, Surendra Prabhawa, Olov Norlén, Per Hellman, Peter Stålberg, Gunnar Westin
BACKGROUND: Small intestinal neuroendocrine tumors (SI-NETs) originate from enterochromaffin cells scattered in the intestinal mucosa of the ileum and jejunum. Loss of one copy of chromosome 18 is the most frequent observed aberration in primary tumors and metastases. The aim of this study was to investigate possible involvement of 5-hydroxymethylcytosine (5hmC), TET1 and TET2 in SI-NETs. METHODS: The analysis was conducted using 40 primary tumors and corresponding 47 metastases...
July 25, 2018: BMC Cancer
Evgeny N Kozlov, Elena U Martynova, Vladimir I Popenko, Coby Schal, Dmitry V Mukha
Densovirus genome replication and capsid assembly take place in the nucleus of the infected cells. However, the mechanisms underlying such processes as the delivery of virus proteins to the nucleus and the export of progeny virus from the nucleus remain elusive. It is evident that nuclear transport signals should be involved in these processes. We performed an in silico search for the putative nuclear localization signal (NLS) and nuclear export signal (NES) motifs in the capsid proteins of the Blattella germanica Densovirus 1 (BgDV1) densovirus...
July 14, 2018: Viruses
Oliver J Gruss
Sexual reproduction requires the generation of gametes, which are highly specialised for fertilisation. Female reproductive cells, oocytes, grow up to large sizes when they accumulate energy stocks and store proteins as well as mRNAs to enable rapid cell divisions after fertilisation. At the same time, metazoan oocytes eliminate their centrosomes, i.e., major microtubule-organizing centres (MTOCs), during or right after the long growth phases. Centrosome elimination poses two key questions: first, how can the centrosome be re-established after fertilisation? In general, metazoan oocytes exploit sperm components, i...
July 10, 2018: Cells
Jacek Hawiger
Sepsis is one of the ten leading causes of death in developed and developing countries. In the United States, sepsis mortality approaches that of acute myocardial infarction and exceeds deaths from stroke. Neonates and the elderly are the most vulner-able patients, with these groups suffering from the highest sepsis mortality. In both groups, many survivors respectively display serious developmental disabilities and cognitive decline. The National Institute of Health/National Heart, Lung, and Blood Institute Panel redefined sepsis as a "severe endothelial dysfunction syndrome in response to intravascular and extravascular infections causing reversible or irreversible injury to the microcirculation responsible for multiple organ failure...
2018: Kardiologia Polska
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