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https://www.readbyqxmd.com/read/29785072/insights-from-the-molecular-modelling-and-docking-analysis-of-aif-nls-complex-to-infer-nuclear-translocation-of-the-protein
#1
Akash Srivaths, Shyam Ramanathan, Seethalakshmi Sakthivel, Skm Habeeb
Apoptosis Inducing Factor protein has a dual role depending on its localization in mitochondrion (energy production) and nucleus (induces apoptosis). Cell damage transports this protein to nucleus which otherwise favors mitochondrion. The alteration of Nuclear Localisation Signal tags could aid nuclear translocation. In this study, apoptosis inducing factor protein (AIF) was conjugated with strong NLS tags and its binding affinity with Importin was studied using in silico approaches such as molecular modeling and docking...
2018: Bioinformation
https://www.readbyqxmd.com/read/29781763/new-insights-into-the-nucleolar-localization-of-a-plant-rna-virus-encoded-protein-that-acts-in-both-rna-packaging-and-rna-silencing-suppression-involvement-of-importins-alpha-and-relevance-for-viral-infection
#2
Miryam Pérez-Cañamás, Carmen Hernández
Despite replication of plus strand RNA viruses takes place in the cytoplasm of host cells, different proteins encoded by these infectious agents have been shown to localize in the nucleus, with high accumulation at the nucleolus. In most cases, the molecular determinants and/or biological significance of such subcellular localization remain elusive. Recently, we reported that protein p37 encoded by Pelargonium line pattern virus (family Tombusviridae) acts in both RNA packaging and RNA silencing suppression...
May 21, 2018: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/29781035/knockdown-of-kpna2-inhibits-autophagy-in-oral-squamous-cell-carcinoma-cell-lines-by-blocking-p53-nuclear-translocation
#3
Feng Lin, Li Gao, Zhenyu Su, Xiaofang Cao, Yuanbo Zhan, Ying Li, Bin Zhang
Oral squamous cell carcinoma (OSCC), one of the 10 most common types of neoplasms in the US, constitutes ~90% of all cases of oral malignancies. Chemoresistance and metastasis are difficult to avoid during the course of treatment, leading to a poor prognosis and a high mortality rate for patients with OSCC. Autophagy, a critical conserved cellular process, has been reported to be highly associated with the regulation of chemoresistance and metastasis of cancer cells. The present study investigated the role of karyopherin α2 (KPNA2), a member of the importin α family, which may serve an important role in p53 nucleocytoplasmic transport in the process of OSCC autophagy...
May 17, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29769639/a-novel-cell-penetrating-peptide-protects-against-neuron-apoptosis-after-cerebral-ischemia-by-inhibiting-the-nuclear-translocation-of-annexin-a1
#4
Xing Li, Lu Zheng, Qian Xia, Lu Liu, Meng Mao, Huijuan Zhou, Yin Zhao, Jing Shi
Nuclear translocation of annexin A1 (ANXA1) has recently been reported to participate in neuronal apoptosis after cerebral ischemia. Prevention of the nuclear translocation of ANXA1 should therefore inhibit neuronal apoptosis and protect against cerebral stroke. Here, we found that, in the repeat III domain of ANXA1, the amino-acid residues from R228 to F237 function as a unique nuclear translocation signal (NTS) and are required for nuclear translocation of ANXA1. Intriguingly, we synthesized a cell-penetrating peptide derived by conjugating the trans-activator of transcription (Tat) domain to the NTS sequence...
May 16, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29765550/mtbp-inhibits-the-erk1-2-elk-1-signaling-in-hepatocellular-carcinoma
#5
Atul Ranjan, Swathi V Iyer, Christopher Ward, Tim Link, Francisco J Diaz, Animesh Dhar, Ossama W Tawfik, Steven A Weinman, Yoshiaki Azuma, Tadahide Izumi, Tomoo Iwakuma
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have performed unbiased luciferase reporter-based signal array analyses and found that MTBP suppresses the activity of the ETS-domain transcription factor Elk-1, a downstream target of Erk1/2 MAP kinases...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29764995/retraction-for-zehorai-and-seger-beta-like-importins-mediate-the-nuclear-translocation-of-mitogen-activated-protein-kinases
#6
Eldar Zehorai, Rony Seger
No abstract text is available yet for this article.
June 1, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29750988/contribution-of-the-residue-at-position-4-within-classical-nuclear-localization-signals-to-modulating-interaction-with-importins-and-nuclear-targeting
#7
Kate M Smith, Veronica Di Antonio, Luca Bellucci, David R Thomas, Fabiana Caporuscio, Francesco Ciccarese, Hanieh Ghassabian, Kylie M Wagstaff, Jade K Forwood, David A Jans, Giorgio Palù, Gualtiero Alvisi
Nuclear import involves the recognition by importin (IMP) superfamily members of nuclear localization signals (NLSs) within protein cargoes destined for the nucleus, the best understood being recognition of classical NLSs (cNLSs) by the IMPα/β1 heterodimer. Although the cNLS consensus [K-(K/R)-X-(K/R) for positions P2-P5] is generally accepted, recent studies indicated that the contribution made by different residues at the P4 position can vary. Here, we apply a combination of microscopy, molecular dynamics, crystallography, in vitro binding, and bioinformatics approaches to show that the nature of residues at P4 indeed modulates cNLS function in the context of a prototypical Simian Virus 40 large tumor antigen-derived cNLS (KKRK, P2-5)...
May 8, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29750782/hey1-and-p53-dependent-trkc-proapoptotic-activity-controls-neuroblastoma-growth
#8
Marie Ménard, Clélia Costechareyre, Gabriel Ichim, Jonathan Blachier, David Neves, Loraine Jarrosson-Wuilleme, Reinhard Depping, Jan Koster, Pierre Saintigny, Patrick Mehlen, Servane Tauszig-Delamasure
The neurotrophin-3 (NT-3) receptor tropomyosin receptor kinase C (TrkC/NTRK3) has been described as a dependence receptor and, as such, triggers apoptosis in the absence of its ligand NT-3. This proapoptotic activity has been proposed to confer a tumor suppressor activity to this classic tyrosine kinase receptor (RTK). By investigating interacting partners that might facilitate TrkC-induced cell death, we have identified the basic helix-loop-helix (bHLH) transcription factor Hey1 and importin-α3 (karyopherin alpha 4 [KPNA4]) as direct interactors of TrkC intracellular domain, and we show that Hey1 is required for TrkC-induced apoptosis...
May 11, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29748336/xpo7-is-a-broad-spectrum-exportin-and-a-nuclear-import-receptor
#9
Metin Aksu, Tino Pleiner, Samir Karaca, Christin Kappert, Heinz-Jürgen Dehne, Katharina Seibel, Henning Urlaub, Markus T Bohnsack, Dirk Görlich
Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates...
May 10, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29748335/nuclear-transport-adapts-to-varying-heat-stress-in-a-multistep-mechanism
#10
Yutaka Ogawa, Naoko Imamoto
Appropriate cell growth conditions are limited to a narrow temperature range. Once the temperature is out of this range, cells respond to protect themselves, but temperature thresholds at which various intracellular responses occur, including nuclear transport systems, remain unclear. Using a newly developed precise temperature shift assay, we found that individual transport pathways have different sensitivities to a rise in temperature. Nuclear translocations of molecular chaperone HSP70s occur at a much lower temperature than the inhibition of Ran-dependent transport...
May 10, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29742803/septin-9-isoform-1-sept9_i1-specifically-interacts-with-importin-%C3%AE-7-to-drive-hypoxia-inducible-factor-hif-1%C3%AE-nuclear-translocation
#11
Keren Tazat, Susanne Schindler, Reinhard Deppeing, Nicola J Mabjeesh
We have shown previously that septin 9 isoform 1 (SEPT9_i1) protein associates with hypoxia-inducible factor (HIF)-1α to augment HIF-1 transcriptional activity by driving its importin-α-mediated nuclear translocation. Using in vitro and in vivo binding assays we identified that HIF-1α interacts with importin-α5 and importin-α7 in prostate cancer cells but only importin-α7 interacts with SEPT9_i1. The interaction with importin-α7 was dependent on the first 25 amino acids of SEPT9_i1 that are unique compared to other members of the mammalian septin family...
May 9, 2018: Cytoskeleton
https://www.readbyqxmd.com/read/29734393/orientia-tsutsugamushi-uses-two-ank-effectors-to-modulate-nf-%C3%AE%C2%BAb-p65-nuclear-transport-and-inhibit-nf-%C3%AE%C2%BAb-transcriptional-activation
#12
Sean M Evans, Kyle G Rodino, Haley E Adcox, Jason A Carlyon
Orientia tsutsugamushi causes scrub typhus, a potentially fatal infection that threatens over one billion people. Nuclear translocation of the transcription factor, NF-κB, is the central initiating cellular event in the antimicrobial response. Here, we report that NF-κB p65 nuclear accumulation and NF-κB-dependent transcription are inhibited in O. tsutsugamushi infected HeLa cells and/or primary macrophages, even in the presence of TNFα. The bacterium modulates p65 subcellular localization by neither degrading it nor inhibiting IκBα degradation...
May 7, 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29722104/long-noncoding-rna-norad-regulates-transforming-growth-factor-%C3%AE-signaling-and-epithelial-to-mesenchymal-transition-like-phenotype
#13
Natsumi Kawasaki, Toshiki Miwa, Satoshi Hokari, Tsubasa Sakurai, Kazuho Ohmori, Kensuke Miyauchi, Kohei Miyazono, Daizo Koinuma
Long noncoding RNAs are involved in a variety of cellular functions. In particular, an increasing number of studies have revealed the functions of long noncoding RNAs in various cancers; however, their precise roles and mechanisms of action remain to be elucidated. NORAD, a cytoplasmic long noncoding RNA, is upregulated by irradiation and functions as a potential oncogenic factor by binding and inhibiting Pumilio proteins (PUM1/PUM2). Here, we show that NORAD upregulates transforming growth factor-β (TGF-β) signaling and regulates TGF-β-induced epithelial-to-mesenchymal transition (EMT)-like phenotype, which is a critical step in the progression of lung adenocarcinoma, A549 cells...
May 2, 2018: Cancer Science
https://www.readbyqxmd.com/read/29721093/graphene-oxide-sensitizes-cancer-cells-to-chemotherapeutics-by-inducing-early-autophagy-events-promoting-nuclear-trafficking-and-necrosis
#14
Kuan-Chen Lin, Mei-Wei Lin, Mu-Nung Hsu, Guan Yu-Chen, Yu-Chan Chao, Hsing-Yu Tuan, Chi-Shiun Chiang, Yu-Chen Hu
Rationale: Cisplatin (CDDP) is a broad-spectrum anticancer drug but chemoresistance to CDDP impedes its wide use for cancer therapy. Autophagy is an event occurring in the cytoplasm and cytoplasmic LC3 puncta formation is a hallmark of autophagy. Graphene oxide (GO) is a nanomaterial that provokes autophagy in CT26 colon cancer cells and confers antitumor effects. Here we aimed to evaluate whether combined use of GO with CDDP (GO/CDDP) overcomes chemoresistance in different cancer cells and uncover the underlying mechanism...
2018: Theranostics
https://www.readbyqxmd.com/read/29717156/high-basolateral-glucose-increases-sodium-glucose-cotransporter-2-and-reduces-sirtuin-1-in-renal-tubules-through-glucose-transporter-2-detection
#15
Hiroyuki Umino, Kazuhiro Hasegawa, Hitoshi Minakuchi, Hirokazu Muraoka, Takahisa Kawaguchi, Takeshi Kanda, Hirobumi Tokuyama, Shu Wakino, Hiroshi Itoh
Under diabetic conditions, sodium-glucose cotransporter 2 (SGLT2) for glucose uptake in proximal tubules (PTs) increases, whereas NAD+ -dependent protein deacetylase silent mating type information regulation 2 homolog 1 (Sirtuin-1; SIRT1) for PT survival decreases. Therefore, we hypothesized that increased glucose influx by SGLT2 reduces SIRT1 expression. To test this hypothesis, db/db mice with diabetes and high-glucose (HG)-cultured porcine PT LLC-PK1 cells in a two-chamber system were treated with the SGLT2 inhibitor canagliflozin...
May 1, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29717109/substitution-of-d701n-in-the-pb2-protein-could-enhance-the-viral-replication-and-pathogenicity-of-eurasian-avian-like-h1n1-swine-influenza-viruses
#16
Suli Liu, Wenfei Zhu, Zhaomin Feng, Rongbao Gao, Junfeng Guo, Xiyan Li, Jia Liu, Dayan Wang, Yuelong Shu
Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses (SIVs) have become predominant in pig populations in China and have recently been reported to have the most potential to raise the next pandemic in humans. The mutation D701N in the PB2 protein, which accounts for 31% of H1N1 SIVs, has previously been shown to contribute to the adaptation of the highly pathogenic H5N1 or H7N7 avian influenza viruses in mammals. However, little is known of the effects of this substitution on the EA H1N1 viruses. Herein, we investigated the contributions of 701N in the PB2 protein to an EA H1N1 SIV (A/Hunan/42443/2015(H1N1), HuN EA-H1N1), which had 701D in the PB2 protein...
May 2, 2018: Emerging Microbes & Infections
https://www.readbyqxmd.com/read/29700284/mutation-of-ipo13-causes-recessive-ocular-coloboma-microphthalmia-and-cataract
#17
Xiu-Feng Huang, Lue Xiang, Wan Cheng, Fei-Fei Cheng, Kai-Wen He, Bo-Wen Zhang, Si-Si Zheng, Ru-Yi Han, Yi-Han Zheng, Xiao-Tao Xu, Huan-Yun Yu, Wenjuan Zhuang, Yuk Fai Leung, Zi-Bing Jin
Ocular coloboma is a developmental structural defect of the eye that often occurs as complex ocular anomalies. However, its genetic etiology remains largely unexplored. Here we report the identification of mutation (c.331C>T, p.R111C) in the IPO13 gene in a consanguineous family with ocular coloboma, microphthalmia, and cataract by a combination of whole-exome sequencing and homozygosity mapping. IPO13 encodes an importin-B family protein and has been proven to be associated with the pathogenesis of coloboma and microphthalmia...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29694900/importin-%C3%AE-and-vnebd-control-meiotic-spindle-disassembly-in-fission-yeast
#18
Ignacio Flor-Parra, Ana Belén Iglesias-Romero, Silvia Salas-Pino, Rafael Lucena, Juan Jimenez, Rafael R Daga
In metazoans, the nuclear envelope (NE) breakdown (NEBD) occurs during "open" mitosis and meiosis. In the fission yeast Schizosaccharomyces pombe, the mitosis and the first meiotic division (MI) are "closed," during which the NE is maintained. Intriguingly, during the second meiotic division (MII), the NE is also maintained, but nuclear and cytoplasmic molecules are mixed similarly to open mitosis, a phenomenon of unknown biological significance called "virtual" NEBD (vNEBD). Here, we show that importin-α-dependent nucleocytoplasmic transport regulates spindle disassembly late in anaphase B at MI, as previously reported for mitosis...
April 24, 2018: Cell Reports
https://www.readbyqxmd.com/read/29677513/nuclear-import-receptor-inhibits-phase-separation-of-fus-through-binding-to-multiple-sites
#19
Takuya Yoshizawa, Rustam Ali, Jenny Jiou, Ho Yee Joyce Fung, Kathleen A Burke, Seung Joong Kim, Yuan Lin, William B Peeples, Daniel Saltzberg, Michael Soniat, Jordan M Baumhardt, Rudolf Oldenbourg, Andrej Sali, Nicolas L Fawzi, Michael K Rosen, Yuh Min Chook
Liquid-liquid phase separation (LLPS) is believed to underlie formation of biomolecular condensates, cellular compartments that concentrate macromolecules without surrounding membranes. Physical mechanisms that control condensate formation/dissolution are poorly understood. The RNA-binding protein fused in sarcoma (FUS) undergoes LLPS in vitro and associates with condensates in cells. We show that the importin karyopherin-β2/transportin-1 inhibits LLPS of FUS. This activity depends on tight binding of karyopherin-β2 to the C-terminal proline-tyrosine nuclear localization signal (PY-NLS) of FUS...
April 19, 2018: Cell
https://www.readbyqxmd.com/read/29677512/nuclear-import-receptors-reverse-aberrant-phase-transitions-of-rna-binding-proteins-with-prion-like-domains
#20
Lin Guo, Hong Joo Kim, Hejia Wang, John Monaghan, Fernande Freyermuth, Julie C Sung, Kevin O'Donovan, Charlotte M Fare, Zamia Diaz, Nikita Singh, Zi Chao Zhang, Maura Coughlin, Elizabeth A Sweeny, Morgan E DeSantis, Meredith E Jackrel, Christopher B Rodell, Jason A Burdick, Oliver D King, Aaron D Gitler, Clotilde Lagier-Tourenne, Udai Bhan Pandey, Yuh Min Chook, J Paul Taylor, James Shorter
RNA-binding proteins (RBPs) with prion-like domains (PrLDs) phase transition to functional liquids, which can mature into aberrant hydrogels composed of pathological fibrils that underpin fatal neurodegenerative disorders. Several nuclear RBPs with PrLDs, including TDP-43, FUS, hnRNPA1, and hnRNPA2, mislocalize to cytoplasmic inclusions in neurodegenerative disorders, and mutations in their PrLDs can accelerate fibrillization and cause disease. Here, we establish that nuclear-import receptors (NIRs) specifically chaperone and potently disaggregate wild-type and disease-linked RBPs bearing a NLS...
April 19, 2018: Cell
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