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"Nuclear Transport"

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...
July 28, 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 (PKA) 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...
July 25, 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 vulnerable 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...
July 12, 2018: Kardiologia Polska
Aili Li, Qingqing Wang, Gaofeng He, Junfei Jin, Guojin Huang
A previous study revealed that DEP domain containing 1 (DEPDC1) is involved in the carcinogenesis of bladder cancer via forming a complex with zinc finger protein 224 (ZNF224) to suppress A20 expression, resulting in the activation of the nuclear factor (NF)-κB signaling pathway; however, the role of DEPDC1 in liver cancer remains unclear. Hep G2 cells were treated with 11R-DEP: 611-628, a peptide capable of disrupting the DEPDC1-ZNF224 complex. Cell proliferation was examined using an MTT assay and apoptosis was analyzed via detection of the apoptotic marker caspase-3 using western blot analysis...
July 2018: Oncology Letters
Steffen Frey, Renate Rees, Jürgen Schünemann, Sheung Chun Ng, Kevser Fünfgeld, Trevor Huyton, Dirk Görlich
Nuclear pore complexes (NPCs) conduct nucleocytoplasmic transport through an FG domain-controlled barrier. We now explore how surface-features of a mobile species determine its NPC passage rate. Negative charges and lysines impede passage. Hydrophobic residues, certain polar residues (Cys, His), and, surprisingly, charged arginines have striking translocation-promoting effects. Favorable cation-π interactions between arginines and FG-phenylalanines may explain this apparent paradox. Application of these principles to redesign the surface of GFP resulted in variants that show a wide span of transit rates, ranging from 35-fold slower than wild-type to ∼500 times faster, with the latter outpacing even naturally occurring nuclear transport receptors (NTRs)...
June 28, 2018: Cell
Jing Guo, Xianxian Liu, Chuanjian Wu, Jingping Hu, Ke Peng, Li Wu, Sidong Xiong, Chunsheng Dong
HIV-1 hijacks host classical cargo nuclear transportation, or nonclassical pathways by directly interacting with importin-β family proteins or nucleoporins for efficient pre-integration complex (PIC) nuclear import. Recently, an N-terminal truncated form of nucleoporin Pom121c (601-987 aa) was reported to inhibit HIV-1 replication. In contrast, we found that HIV-1 replication was significantly decreased in 293T and TZM-b1 cells with siRNA-mediated Pom121 knockdown. Quantitative PCR indicated that viral replication was impaired at the step of cDNA nuclear import...
June 25, 2018: Virology
Thomas W Kirby, Lars C Pedersen, Scott A Gabel, Natalie R Gassman, Robert E London
Despite the essential roles of pol X family enzymes in DNA repair, information about the structural basis of their nuclear import is limited. Recent studies revealed the unexpected presence of a functional nuclear localization signal (NLS) in DNA polymerase β, indicating the importance of active nuclear targeting, even for enzymes likely to leak into and out of the nucleus. The current studies further explore the active nuclear transport of these enzymes by identifying and structurally characterizing the functional NLS sequences in the three remaining human pol X enzymes: terminal deoxynucleotidyl transferase (TdT), DNA polymerase mu (pol μ) and DNA polymerase lambda (pol λ)...
June 22, 2018: Traffic
Ta Sun, Fanqi Wang, Wen Pan, Qihan Wu, Jingwen Wang, Jianfeng Dai
Ticks, blood-feeding arthropods, and secrete immunosuppressive molecules that inhibit host immune responses and provide survival advantages to pathogens. In this study, we characterized the immunosuppressive function of a novel tick salivary protein, DsCystatin, from Dermacentor silvarum of China. DsCystatin directly interacted with human Cathepsins L and B and inhibited their enzymatic activities. DsCystatin impaired the expression of inflammatory cytokines such as IL1β, IFNγ, TNFα, and IL6 from mouse bone marrow-derived macrophages (BMDMs) that had been stimulated with LPS or Borrelia burgdorferi ...
2018: Frontiers in Immunology
Lan Hainan, Liu Huilin, Mahamad Khan, Zheng Xin, Yang YuJiang, Zhang Hui, Yao Naiquan
Traditional views suggest that growth hormone and the growth hormone receptor (GH/GHR complex) exert their functions only on the plasma membrane. This paradigm, however, has been challenged by recent new findings that the GH/GHR complex could translocate into cell nuclei where they could still exhibit important physiological functions. We also reported the nuclear localization of porcine GH/GHR and their potential functions in porcine hepatocytes. However, the basic path of pGH/GHR's nuclear translocation remains unclear...
June 8, 2018: General and Comparative Endocrinology
Masaaki Iwamoto, Chie Mori, Hiroko Osakada, Takako Koujin, Yasushi Hiraoka, Tokuko Haraguchi
Ciliated protozoa possess two morphologically and functionally distinct nuclei: a macronucleus (MAC) and a micronucleus (MIC). The MAC is transcriptionally active and functions in all cellular events. The MIC is transcriptionally inactive during cell growth, but functions in meiotic events to produce progeny nuclei. Thus, these two nuclei must be distinguished by the nuclear proteins required for their distinct functions during cellular events such as cell proliferation and meiosis. To understand the mechanism of the nuclear transport specific to either MAC or MIC, we identified specific nuclear localization signals (NLSs) in two MAC- and MIC-specific nuclear proteins, macronuclear histone H1 and micronuclear linker histone-like protein (Mlh1), respectively...
July 2018: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
Moé Yamada, Gohta Goshima
Long-distance transport along microtubules (MTs) is critical for intracellular organisation. In animals, antagonistic motor proteins kinesin (plus end-directed) and dynein (minus end-directed) drive cargo transport. In land plants, however, the identity of motors responsible for transport is poorly understood, as genes encoding cytoplasmic dynein are absent in plant genomes. How other functions of dynein are brought about in plants also remains unknown. Here, we show that a subclass of the kinesin-14 family, KCH (kinesin with calponin homology domain)-which can also bind actin-drives MT minus end-directed nuclear transport in the moss Physcomitrella patens...
June 7, 2018: Plant Cell
Daniela Castanotto, Xiaowei Zhang, Jessica Alluin, Xizhe Zhang, Jacqueline Rüger, Brian Armstrong, John Rossi, Arthur Riggs, C A Stein
Although some information is available for specific subsets of miRNAs and several factors have been shown to bind oligonucleotides (ONs), no general transport mechanism for these molecules has been identified to date. In this work, we demonstrate that the nuclear transport of ONs, siRNAs, and miRNAs responds to cellular stress. Furthermore, we have identified a stress-induced response complex (SIRC), which includes Ago-1 and Ago-2 in addition to the transcription and splicing regulators YB1, CTCF, FUS, Smad1, Smad3, and Smad4...
June 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Moon Y F Tay, Subhash G Vasudevan
Dengue virus (DENV) replication occurs in virus-induced vesicles that contain the replication complex (RC) where viral RNA, viral proteins and host proteins participate in RNA-RNA, RNA-protein and protein-protein interactions to ensure viral genome synthesis. However, the details of the multitude of interactions involved in the biogenesis of the infectious virion are not fully understood. In this review, we will focus on the interaction between non-structural (NS) proteins NS3 and NS5, as well as their interactions with viral RNA and briefly also the interaction of NS5 with the host nuclear transport receptor protein importin-α...
2018: Advances in Experimental Medicine and Biology
Guojun Chen, Ben Ma, Yuyuan Wang, Shaoqin Gong
The long-sought promise of gene therapy for the treatment of human diseases remains unfulfilled, largely hindered by the lack of an efficient and safe delivery vehicle. In this study, we have developed a universal glutathione-responsive nanoplatform for the efficient delivery of negatively charged genetic biomacromolecules. The cationic block copolymer, poly(aspartic acid-(2-aminoethyl disulfide)-(4-imidazolecarboxylic acid))-poly(ethylene glycol), bearing imidazole residues and disulfide bonds, can form polyplexes with negatively charged DNA, mRNA, and Cas9/sgRNA ribonucleoprotein (RNP) through electrostatic interactions, which enable efficient cellular uptake, endosomal escape, and cytosol unpacking of the payloads...
June 6, 2018: ACS Applied Materials & Interfaces
Heying Cui, Kyle M Loftus, Crystal R Noell, Sozanne R Solmaz
Cyclin-dependent kinase 1 (Cdk1) is a master controller for the cell cycle in all eukaryotes and phosphorylates an estimated 8 - 13% of the proteome; however, the number of identified targets for Cdk1, particularly in human cells is still low. The identification of Cdk1-specific phosphorylation sites is important, as they provide mechanistic insights into how Cdk1 controls the cell cycle. Cell cycle regulation is critical for faithful chromosome segregation, and defects in this complicated process lead to chromosomal aberrations and cancer...
May 3, 2018: Journal of Visualized Experiments: JoVE
Poonam Dhillon, Varsha N Tandra, Sandip G Chorghade, Nima D Namsa, Lipika Sahoo, C Durga Rao
Rotavirus replicates in the cytoplasm of infected cells in unique virus-induced cytoplasmic inclusion bodies called viroplasms (VMs), which are nucleated by two essential viral nonstructural proteins, NSP2 and NSP5. However, the precise composition of the VM, the intracellular localization of host proteins during virus infection, and their association with VMs or role in rotavirus growth remained largely unexplored. Mass spectrometry analyses revealed the presence of several host heterogeneous nuclear ribonucleoproteins (hnRNPs), AU-rich element-binding proteins (ARE-BPs), and cytoplasmic proteins from uninfected MA104 cell extracts in the pulldown (PD) complexes of the purified viroplasmic proteins NSP2 and NSP5...
August 1, 2018: Journal of Virology
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