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"Nuclear Transport"

Jian Yang, Yuqi Guo, Cuijie Lu, Ruohan Zhang, Yaoyu Wang, Liang Luo, Yanli Zhang, Catherine H Chu, Katherine J Wang, Sabrine Obbad, Wenbo Yan, Xin Li
Prostate cancer (PCa) initiation and progression requires activation of numerous oncogenic signaling pathways. Nuclear-cytoplasmic transport of oncogenic factors is mediated by Karyopherin proteins during cell transformation. However, the role of nuclear transporter proteins in PCa progression has not been well defined. Here, we report that the KPNB1, a key member of Karyopherin beta subunits, is highly expressed in advanced prostate cancers. Further study showed that targeting KPNB1 suppressed the proliferation of prostate cancer cells...
February 11, 2019: Oncogene
Yoshiyuki Hakata, Hiroyuki Michiue, Takashi Ohtsuki, Masaaki Miyazawa, Mizuki Kitamatsu
We synthesized a pair of compounds containing leucine zipper peptides to deliver protein cargo into cells. One is a cell-penetrating peptide (CPP) with Lz(E), a leucine zipper peptide containing negatively charged amino acids, and the other is a Nanog protein with Lz(K), a leucine zipper peptide containing positively charged amino acids. When cells were treated with these equimolar mixtures, Nanog-Lz(K) hybridized with Lz(E)-CPP was successfully delivered into the cells. Furthermore, Nanog-Lz(K) exerted its proper function after nuclear transport...
February 4, 2019: Bioorganic & Medicinal Chemistry Letters
Ankur Mishra, Wouter Sipma, Liesbeth M Veenhoff, Erik Van der Giessen, Patrick R Onck
Nuclear pore complexes (NPCs) are large protein complexes embedded in the nuclear envelope separating the cytoplasm from the nucleoplasm in eukaryotic cells. They function as selective gates for the transport of molecules in and out of the nucleus. The inner wall of the NPC is coated with intrinsically disordered proteins rich in phenylalanine-glycine repeats (FG-repeats), which are responsible for the intriguing selectivity of NPCs. The phosphorylation state of the FG-Nups is controlled by kinases and phosphatases...
January 30, 2019: International Journal of Molecular Sciences
Edward A Lemke, Aritra Chowdhury, Sergey A Kovalenko, Iker V Aramburu, Piau S Tan, Nikolaus P Ernsting
Recognition of Intrinsically Disordered Proteins (IDPs) is highly dependent on dynamics owing to the lack of structure. Here we studied the interplay between dynamics and molecular recognition in IDPs with a combination of time-resolving tools from femtoseconds to nanoseconds. We interrogated conformational dynamics and surface water dynamics and its attenuation upon partner binding using two IDPs, IBB and Nup153FG, both of central relevance to the nucleocytoplasmic transport machinery. These proteins bind the same nuclear transport receptor (Importinβ) with drastically different binding mechanisms, coupled folding-binding and fuzzy complex formation respectively...
January 31, 2019: Angewandte Chemie
Dapeng Yun, Hongxiang Wang, Yuqi Wang, Yuanyuan Chen, Zhipeng Zhao, Jiawei Ma, Yuanyuan Ji, Qilin Huang, Juxiang Chen, Hongyan Chen, Daru Lu
BACKGROUND: Glioma is the most common and aggressive primary brain tumor with polygenic susceptibility. The cytoplasmic/nuclear shuttling protein, SLC2A4RG (SLC2A4 regulator), has been identified in the 20q13.33 region influencing glioma susceptibility by genome-wide association studies (GWAS) and fine mapping analyses. METHODS: To discover the expression of SLC2A4RG and its relationship with patient prognosis, tissue microarray containing glioma samples and normal brains was constructed followed by immunohistochemical staining...
January 24, 2019: EBioMedicine
Amélie Donchet, Justine Oliva, Alice Labaronne, Laura Tengo, Myriam Miloudi, Francine C A Gerard, Caroline Mas, Guy Schoehn, Rob W H Ruigrok, Mariette Ducatez, Thibaut Crépin
This paper focuses on the nucleoprotein (NP) of the newly identified member of the Orthomyxoviridae family, Influenza D virus. To date several X-ray structures of NP of Influenza A (A/NP) and B (B/NP) viruses and of infectious salmon anemia (ISA/NP) virus have been solved. Here we purified, characterized and solved the X-ray structure of the tetrameric D/NP at 2.4 Å resolution. The crystal structure of its core is similar to NP of other Influenza viruses. However, unlike A/NP and B/NP which possess a flexible amino-terminal tail containing nuclear localization signals (NLS) for their nuclear import, D/NP possesses a carboxy-terminal tail (D/NPTAIL )...
January 24, 2019: Scientific Reports
Robert J Andrew, Kate Fisher, Kate J Heesom, Katherine A B Kellett, Nigel M Hooper
The generation of the amyloid-β (Aβ) peptides from the amyloid precursor protein (APP) through sequential proteolysis by β- and γ-secretases is a key pathological event in the initiation and propagation of Alzheimer's disease. Aβ and the transcriptionally active APP intracellular domain (AICD) are generated preferentially from the APP695 isoform compared to the longer APP751 isoform. As the Aβ and AICD produced from cleavage of APP695 and APP751 are identical we hypothesised that the two isoforms have differences within their interactomes which mediate the differential processing of the two isoforms...
January 21, 2019: Journal of Neurochemistry
Doudou Luo, Yali Zhang, Xiaoqian Yuan, Yilin Pan, Lichao Yang, Yun Zhao, Rengong Zhuo, Caixia Chen, Lu Pen, Wenjun Li, Xin Jin, Yu Zhou
Glial activation and scar formation impede the neurological function recovery after cerebral ischemia. Oleoylethanolamide (OEA), a bioactive lipid mediator, shows neuroprotection against acute brain ischemia, however, its long-term effect, especially on glial scar formation, has not been characterized. In this research, we investigate the effect of OEA on glial activation and scar formation after cerebral ischemia in vitro and in vivo experiments. Glial scar formation in vitro model was induced by transforming growth factor β1 (TGF-β1) in C6 glial cell culture, and experiment model in vivo was induced by middle cerebral artery occlusion (MCAO) in mice...
January 17, 2019: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
Jing-Jing Wu, Xiao-Mei Yuan, Chao Huang, Guo-Yin An, Zhan-Ling Liao, Guang-An Liu, Run-Xiang Chen
Inducible nitric oxide synthase (iNOS) is a molecule critical for the development of inflammation-associated disorders. Its induction should be tightly controlled in order to maintain cellular homeostasis. Upon lipopolysaccharide (LPS) stimulation, iNOS, in most settings, is induced by the activation of inhibitor of κB-α (IκB-α)-nuclear factor κB (NF-κB) signaling. Farnesyl thiosalicylic acid (FTS), a synthetic small molecule that is considered to detach Ras from the inner cell membrane, has been shown to exhibit numerous anti-inflammatory functions...
January 15, 2019: International Immunopharmacology
Xinglong Wang, Changjie Lv, Xiaojuan Ji, Bin Wang, Li Qiu, Zengqi Yang
Porcine circovirus 2 (PCV2) capsid protein (Cap) has a nuclear localization signal (NLS) and can enter the nucleus. In this study, ivermectin, a small-molecule nuclear import inhibitor of proteins was used to determine the role of nuclear localization of Cap on PCV2 replication. Observation by fluorescence microscopy of the intracellular localization of Cap and Cap NLS in cells cultured with ivermectin (50 µg/mL) determined that Cap and Cap NLS were located in the cytoplasm; in contrast, for cells cultured without ivermectin, they accumulated in the cell nucleus...
January 15, 2019: Virus Research
Marina Blenski, Ralph H Kehlenbach
LRRC59 (leucine-rich repeat-containing protein 59) is a tail-anchored protein with a single transmembrane domain close to its C-terminal end that localizes to the endoplasmic reticulum (ER) and the nuclear envelope. Here, we investigate the mechanisms of membrane integration of LRRC59 and its targeting to the inner nuclear membrane (INM). Using purified microsomes, we show that LRRC59 can be post-translationally inserted into ER-derived membranes. The TRC-pathway, a major route for post-translational membrane insertion, is not required for LRRC59...
January 15, 2019: International Journal of Molecular Sciences
Christopher Brownlee, Rebecca Heald
Early embryogenesis is accompanied by reductive cell divisions requiring that subcellular structures adapt to a range of cell sizes. The interphase nucleus and mitotic spindle scale with cell size through both physical and biochemical mechanisms, but control systems that coordinately scale intracellular structures are unknown. We show that the nuclear transport receptor importin α is modified by palmitoylation, which targets it to the plasma membrane and modulates its binding to nuclear localization signal (NLS)-containing proteins that regulate nuclear and spindle size in Xenopus egg extracts...
January 3, 2019: Cell
Yoshimi Asano, Tamotsu Takeuchi, Hiroshi Okubo, Chiemi Saigo, Yusuke Kito, Yoshinori Iwata, Manabu Futamura, Kazuhiro Yoshida
LRP1B intracellular domain is released and transported to the nucleus; however, pathological consequences of this nuclear transport are largely unclear. We aimed to unravel the pathobiological significance of nuclear localization of LRP1B intracellular domain in mammary gland carcinogenesis. Immunohistochemical staining using antibodies for LRP1B intracellular domain was performed to determine LRP1B expression in 92 invasive ductal breast carcinomas. LRP1B immunoreactivity was detected in the surface membrane and cytoplasm of 60 of 92 invasive ductal carcinomas and in the nucleus of 15 of 92 carcinomas...
January 3, 2019: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Ian S Hsu, Bob Strome, Sergei Plotnikov, Alan M Moses
Several examples of transcription factors that show stochastic, unsynchronized pulses of nuclear localization have been described. Here we show that under constant calcium stress, nuclear localization pulses of the transcription factor Crz1 follow stochastic variations in cytoplasmic calcium concentration. We find that the size of the stochastic calcium bursts is positively correlated with the number of subsequent Crz1 pulses. Based on our observations, we propose a simple stochastic model of how the signalling pathway converts a constant external calcium concentration into a digital number of Crz1 pulses in the nucleus, due to the time delay from nuclear transport and the stochastic decoherence of individual Crz1 molecule dynamics...
December 20, 2018: G3: Genes—Genomes—Genetics
Natalia Dworak, Dawid Makosa, Mandovi Chatterjee, Kasey Jividen, Chun-Song Yang, Chelsi Snow, William C Simke, Isaac G Johnson, Joshua B Kelley, Bryce M Paschal
The Ran GTPase regulates nuclear import and export by controlling the assembly state of transport complexes. This involves the direct action of RanGTP, which is generated in the nucleus by the chromatin-associated nucleotide exchange factor, RCC1. Ran interactions with RCC1 contribute to formation of a nuclear:cytoplasmic (N:C) Ran protein gradient in interphase cells. In previous work, we showed that the Ran protein gradient is disrupted in fibroblasts from Hutchinson-Gilford progeria syndrome (HGPS) patients...
December 19, 2018: Aging Cell
Yoon-Dong Park, Joseph N Jarvis, Guowu Hu, Sarah E Davis, Jin Qiu, Nannan Zhang, Christopher Hollingsworth, Angela Loyse, Paul J Gardina, Tibor Valyi-Nagy, Timothy G Myers, Thomas S Harrison, Tihana Bicanic, Peter R Williamson
Human infection with Cryptococcus causes up to a quarter of a million AIDS-related deaths annually and is the most common cause of nonviral meningitis in the United States. As an opportunistic fungal pathogen, Cryptococcus neoformans is distinguished by its ability to adapt to diverse host environments, including plants, amoebae, and mammals. In the present study, comparative transcriptomics of the fungus within human cerebrospinal fluid identified expression profiles representative of low-nutrient adaptive responses...
December 18, 2018: MBio
Richard Bowman, Nathan Balukof, Talitha Ford, Sarit Smolikove
During meiotic prophase I sister chromatid cohesion is established in a way that supports the assembly of the synaptonemal complex (SC). The SC connects homologous chromosomes, directing meiotic recombination to create crossovers. In this paper we identify two proteins that cooperate to import and load meiotic cohesins, thus indirectly promoting SC assembly. AKIR-1 is a protein with a previously identified meiotic role in SC disassembly. akir-1 mutants have no obvious defects in sister chromatid cohesion. We identified ima-2 , a gene encoding for an α-importin nuclear transport protein, as a gene interacting with akir-1 Analysis of akir-1;ima-2 double mutants reveals a decrease in the number of germline nuclei and the formation of polycomplexes (PC) (an SC protein aggregate)...
December 18, 2018: Genetics
Xiao-Yan He, Bo-Ya Liu, Yan Peng, Ren-Xi Zhuo, Si-Xue Cheng
Accurate and efficient delivery of genome editing plasmids to targeted cells is of critical importance in genome editing. Herein, we prepared a multifunctional delivery vector with combination of ligand-mediated selectivity and peptide mediated transmembrane function to effectively deliver plasmids to targeted cancerous cells. In the delivery system, the CRISPR-Cas9 plasmid is combined with protamine with membrane and nuclear translocating activities and co-precipitated with CaCO3, which is further decorated by AS1411 functionalized carboxymethyl chitosan (ACMC) and TAT peptide functionalized carboxymethyl chitosan (TCMC)...
December 12, 2018: ACS Applied Materials & Interfaces
Imke Baade, Ralph H Kehlenbach
The molecular mechanisms of nuclear transport have been described in great detail and we are beginning to understand the structures of transport complexes and even of subcomplexes of the nuclear pore at an atomic or near-atomic resolution. The complexity of the clients that use the transport machinery, by contrast, is less well understood, although some transport receptors are reported to have hundreds of different cargoes and others only a few. Here, we review the recent attempts to define the cargo spectrum of individual nuclear transport receptors using bioinformatic, biochemical and cell biological approaches and compare the results obtained by these complementary methods...
December 6, 2018: Current Opinion in Cell Biology
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
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