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https://www.readbyqxmd.com/read/28325843/a-biochemical-framework-for-eif4e-dependent-mrna-export-and-nuclear-re-cycling-of-the-export-machinery
#1
Laurent Volpon, Biljana Culjkovic-Kraljacic, Hye Seon Sohn, Alexis Blanchett-Cohen, Michael J Osborne, Katherine L B Borden
The eukaryotic translation initiation factor eIF4E acts in the nuclear export and translation of a subset of mRNAs. Both of these functions contribute to its oncogenic potential. While the biochemical mechanisms that underlie translation are relatively well understood, the molecular basis for eIF4E's role in mRNA export remains largely unexplored. To date over 3000 transcripts, many encoding oncoproteins, were identified as potential nuclear eIF4E export targets. These target RNAs typically contain a ~50 nucleotide eIF4E sensitivity element (4ESE) in the 3' UTR and a 7-methylguanosine cap on the 5' end...
March 21, 2017: RNA
https://www.readbyqxmd.com/read/28316180/-effect-and-related-mechanism-of-microrna-181-attenuates-oxidized-low-density-lipoprotein-induced-vascular-endothelial-cell-injury
#2
N N Wang, X Sun, X L Zhang, L Lou, K M Chen, H Li, L Tang, W G Wang, M Zhang
Objective: To observe the expression level of microRNA-181 (miR-181) and importin-α3 in oxidized low density lipoprotein (ox-LDL) induced vascular endothelial cell injury models, and explore the effect and mechanism of miR-181 on endothelial cell injury. Methods: Human vein endothelial cell line CRL-1730 were cultured and vascular endothelial cell injury model was established by intervention with ox-LDL. The cells were divided into control group (intervened by double distilled water), low-dose group (intervened by 10 μg/ml ox-LDL) and high-dose group (intervened by 20 μg/ml ox-LDL)...
March 24, 2017: Zhonghua Xin Xue Guan Bing za Zhi
https://www.readbyqxmd.com/read/28295920/importin-%C3%AE-1-targeting-by-hepatitis-c-virus-ns3-4a-protein-restricts-irf3-and-nf-%C3%AE%C2%BAb-signaling-of-ifnb1-antiviral-response
#3
Bridget Gagné, Nicolas Tremblay, Alex Y Park, Martin Baril, Daniel Lamarre
In this study, newly identified host interactors of hepatitis C virus (HCV) proteins were assessed for a role in modulating innate immune response. The analysis revealed enrichment for components of the nuclear transport machinery and the crucial interaction with NS3/4A protein in suppression of interferon-β (IFNB1) induction. Using a comprehensive microscopy-based high-content screening approach combined to the gene silencing of nuclear transport factors, we showed that NS3/4A-interacting proteins control the nucleocytoplasmic trafficking of IFN regulatory factor 3 (IRF3) and NF-κB p65 upon Sendai virus (SeV) infection...
March 13, 2017: Traffic
https://www.readbyqxmd.com/read/28262749/identification-of-stable-housekeeping-genes-in-response-to-ionizing-radiation-in-cancer-research
#4
Gopal Iyer, Albert R Wang, Sean R Brennan, Shay Bourgeois, Eric Armstrong, Pari Shah, Paul M Harari
Housekeeping genes (HKGs) are essential for basic maintenance of a variety of cellular processes. They ideally maintain uniform expression independent of experimental conditions. However, the effects of ionizing radiation (IR) on HKG expression is unclear. Statistical algorithms, geNorm and Normfinder were used for estimating the stability of HKGs as raw quantification cycle (Cq) values were not a reliable factor for normalization. Head and neck, non-small lung and pancreas cells were exposed to 2, 4 and 6 Gy IR doses and expression of fourteen HKGs was measured at 5 min to 48 h post-irradiation within a given tissue...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28259822/ddx17-nucleocytoplasmic-shuttling-promotes-acquired-gefitinib-resistance-in-non-small-cell-lung-cancer-cells-via-activation-of-%C3%AE-catenin
#5
Kai Li, Chunfen Mo, Di Gong, Yan Chen, Zhao Huang, Yanyan Li, Jie Zhang, Lugang Huang, Yuan Li, Frances V Fuller-Pace, Ping Lin, Yuquan Wei
Although epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are effective for non-small cell lung cancer (NSCLC) patients with EGFR mutations, almost all these patients will eventually develop acquired resistance to EGFR-TKI. However, the molecular mechanisms responsible for gefitinib resistance remain still not fully understood. Here, we report that elevated DDX17 levels are observed in gefitinib-resistant NSCLC cells than gefitinib-sensitive cells. Upregulation of DDX17 enhances the gefitinib resistance, whereas DDX17-silenced cells partially restore gefitinib sensitivity...
March 1, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28258103/protecting-pten-in-the-nucleus
#6
(no author information available yet)
A recent study shows that the transport receptor Importin-11 relocates PTEN, a tumor suppressor, to the nucleus, preventing its degradation in the cytoplasm. Mice lacking Importin-11 are prone to lung cancers, and its absence in human prostate and lung tumors signals a poorer prognosis.
March 3, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28257601/mir181b-3p-and-its-target-importin-%C3%AE-5-regulate-tlr4-signaling-in-kupffer-cells-and-liver-injury-in-mice-in-response-to-ethanol
#7
Paramananda Saikia, Damien Bellos, Megan R McMullen, Katherine A Pollard, Carol de la Motte, Laura E Nagy
Increased inflammatory signaling by Kupffer cells contributes to alcoholic liver disease (ALD). Here we investigated the impact of small-specific sized hyaluronic acid of ∼35kD (HA35) on ethanol-induced sensitization of Kupffer cells, as well as ethanol-induced liver injury in mice. Un-biased analysis of microRNA (miRNA) expression in Kupffer cells identified miRNAs regulated by both ethanol and HA35. TLR4-mediated signaling was assessed in primary cultures of Kupffer cells from ethanol- and pair-fed rats after treatment with HA35...
March 3, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28254634/competitive-regulation-of-ipo4-transcription-by-elk1-and-gabp
#8
Pengpeng Xu, Wenbo Lin, Fenglin Liu, Alan Tartakoff, Tao Tao
Nuclear import is a highly selective process that involves the specific recognition of appropriate import signals by suitable receptors. Many nuclear transport pathways are mediated by importin β superfamily members. Among them, IPO4 is a nuclear import receptor for many cargoes. However, its transcriptional regulation remains largely unknown. In the present study, we identified a core region encompassing nt -118 to +108 that is necessary for its promoter activity. Transcription factors binding to this region were screened, resulting in the identification of two members of the Ets family, Ets-like transcription factor-1 and GA binding protein, which repress or activate its promoter activity, respectively...
February 27, 2017: Gene
https://www.readbyqxmd.com/read/28254629/the-effect-of-nanoparticle-size-and-nls-density-on-nuclear-targeting-in-cancer-and-normal-cells-impaired-nuclear-import-and-aberrant-nanoparticle-intracellular-trafficking-in-glioma
#9
Salma N Tammam, Hassan M E Azzazy, Alf Lamprecht
The cell nucleus is an interesting target in many diseases with particular interest in cancer. Previously, nuclear targeted small and large chitosan nanoparticles (S-NPs≈25nm, and L-NPs≈150nm respectively), modified with low, intermediate and high densities of NLS (L-NLS, I-NLS and H-NLS) were developed and assessed in L929 fibroblasts. However, to evade apoptosis and stimulate tumor growth cancer cells are capable of manipulating the nuclear-cytoplasmic transport on many levels, making NPs that are capable of nuclear targeting in normal cells incapable of doing so in cancer...
February 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28240251/development-of-a-pipeline-for-automated-high-throughput-analysis-of-paraspeckle-proteins-reveals-specific-roles-for-importin-%C3%AE-proteins
#10
Andrew T Major, Yoichi Miyamoto, Camden Y Lo, David A Jans, Kate L Loveland
We developed a large-scale, unbiased analysis method to measure how functional variations in importin (IMP) α2, IMPα4 and IMPα6 each influence PSPC1 and SFPQ nuclear accumulation and their localization to paraspeckles. This addresses the hypothesis that individual IMP protein activities determine cargo nuclear access to influence cell fate outcomes. We previously demonstrated that modulating IMPα2 levels alters paraspeckle protein 1 (PSPC1) nuclear accumulation and affects its localization into a subnuclear domain that affects RNA metabolism and cell survival, the paraspeckle...
February 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28216671/dual-mechanisms-regulate-the-nucleocytoplasmic-localization-of-human-ddx6
#11
Jo-Hsi Huang, Wei-Chi Ku, Yen-Chun Chen, Yi-Ling Chang, Chia-Ying Chu
DDX6 is a conserved DEAD-box protein (DBP) that plays central roles in cytoplasmic RNA regulation, including processing body (P-body) assembly, mRNA decapping, and translational repression. Beyond its cytoplasmic functions, DDX6 may also have nuclear functions because its orthologues are known to localize to nuclei in several biological contexts. However, it is unclear whether DDX6 is generally present in human cell nuclei, and the molecular mechanism underlying DDX6 subcellular distribution remains elusive...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28205572/ran-dependent-tpx2-activation-promotes-acentrosomal-microtubule-nucleation-in-neurons
#12
Wen-Shin Chen, Yi-Ju Chen, Yung-An Huang, Bing-Yuan Hsieh, Ho-Chieh Chiu, Pei-Ying Kao, Chih-Yuan Chao, Eric Hwang
The microtubule (MT) cytoskeleton is essential for the formation of morphologically appropriate neurons. The existence of the acentrosomal MT organizing center in neurons has been proposed but its identity remained elusive. Here we provide evidence showing that TPX2 is an important component of this acentrosomal MT organizing center. First, neurite elongation is compromised in TPX2-depleted neurons. In addition, TPX2 localizes to the centrosome and along the neurite shaft bound to MTs. Depleting TPX2 decreases MT formation frequency specifically at the tip and the base of the neurite, and these correlate precisely with the regions where active GTP-bound Ran proteins are enriched...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28193700/the-nuclear-transport-receptor-importin-11-is-a-tumor-suppressor-that-maintains-pten-protein
#13
Muhan Chen, Dawid G Nowak, Navneet Narula, Brian Robinson, Kaitlin Watrud, Alexandra Ambrico, Tali M Herzka, Martha E Zeeman, Matthias Minderer, Wu Zheng, Saya H Ebbesen, Kendra S Plafker, Carlos Stahlhut, Victoria M Y Wang, Lorna Wills, Abu Nasar, Mireia Castillo-Martin, Carlos Cordon-Cardo, John E Wilkinson, Scott Powers, Raffaella Sordella, Nasser K Altorki, Vivek Mittal, Brendon M Stiles, Scott M Plafker, Lloyd C Trotman
Phosphatase and tensin homologue (PTEN) protein levels are critical for tumor suppression. However, the search for a recurrent cancer-associated gene alteration that causes PTEN degradation has remained futile. In this study, we show that Importin-11 (Ipo11) is a transport receptor for PTEN that is required to physically separate PTEN from elements of the PTEN degradation machinery. Mechanistically, we find that the E2 ubiquitin-conjugating enzyme and IPO11 cargo, UBE2E1, is a limiting factor for PTEN degradation...
March 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28193699/importin-11-keeps-pten-safe-from-harm
#14
Nick R Leslie
In this issue, Chen et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201604025) show that Importin-11 traffics the tumor suppressor PTEN into the nucleus and in so doing protects it from cytoplasmic proteins that cause PTEN degradation. This work helps explain the nuclear accumulation of PTEN observed in many healthy tissues and, because Ipo11 mutant mice develop lung tumors, also implicates Importin-11 as a novel tumor suppressor.
March 6, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28187450/nucleocytoplasmic-shuttling-of-sox14a-and-sox14b-transcription-factors
#15
Zhen-Yu She, Wan-Xi Yang
The nucleocytoplasmic shuttling of SOX transcription factors play a crucial role in the regulation of SOX protein functions during development. In this study, we have demonstrated two nuclear localization signals in the HMG box of Eriocheir sinensis SOX14A and SOX14B. These two conserved nuclear localization signals mediate nuclear transport. The N-termini nuclear localization signal mediates the calmodulin-dependent pathway and the C-termini nuclear localization signal interacts with the importin-β pathway...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187419/dynamics-of-mirna-biogenesis-and-nuclear-transport
#16
Aneesh Kotipalli, Ravikumar Gutti, Chanchal K Mitra
MicroRNAs (miRNAs) are short noncoding RNA sequences ~22 nucleotides in length that play an important role in gene regulation-transcription and translation. The processing of these miRNAs takes place in both the nucleus and the cytoplasm while the final maturation occurs in the cytoplasm. Some mature miRNAs with nuclear localisation signals (NLS) are transported back to the nucleus and some remain in the cytoplasm. The functional roles of these miRNAs are seen in both the nucleus and the cytoplasm. In the nucleus, miRNAs regulate gene expression by binding to the targeted promoter sequences and affect either the transcriptional gene silencing (TGS) or transcriptional gene activation (TGA)...
December 22, 2016: Journal of Integrative Bioinformatics
https://www.readbyqxmd.com/read/28179529/differential-disruption-of-nucleocytoplasmic-trafficking-pathways-by-rhinovirus-2a-proteases
#17
Kelly Watters, Bahar Inankur, Jaye C Gardiner, Jay Warrick, Nathan M Sherer, John Yin, Ann C Palmenberg
The RNA rhinoviruses (RV) encode 2A proteases (2A(pro)) that contribute essential polyprotein processing and host-cell shutoff functions during infection, including the cleavage of Phe/Gly-containing nucleoporin proteins (Nups) within nuclear pore complexes (NPC). Within the 3 RV species, multiple divergent genotypes encode diverse 2A(pro) sequences which act differentially on specific Nups. Since only subsets of Phe/Gly motifs, particularly those within Nup62, Nup98 and Nup153, are recognized by transport receptors (karyopherins) when trafficking large molecular cargos through the NPC, the processing preferences of individual 2A(pro) predict RV genotype-specific targeting of NPC pathways and cargos...
February 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28166455/structural-and-mechanistic-insights-into-nuclear-transport-and-delivery-of-the-critical-pluripotency-factor-oct4-to-dna
#18
Takahide Okuyama, Ryosuke Yamagishi, Jiro Shimada, Masaaki Ikeda, Yayoi Maruoka, Hiroki Kaneko
Oct4 is a master regulator of the induction and maintenance of cellular pluripotency, and has crucial roles in early stages of differentiation. It is the only factor that cannot be substituted by other members of the same protein family to induce pluripotency. However, although Oct4 nuclear transport and delivery to target DNA are critical events for reprogramming to pluripotency, little is known about the molecular mechanism. Oct4 is imported to the nucleus by the classical nuclear transport mechanism, which requires importin α as an adaptor to bind the nuclear localization signal (NLS)...
February 17, 2017: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/28163061/importins-in-the-maintenance-and-lineage-commitment-of-es-cells
#19
REVIEW
Noriko Yasuhara, Yoshihiro Yoneda
The nucleus of a eukaryotic cell is separated from the cytoplasm by a nuclear envelope, and nuclear pores within the envelope facilitate nucleocytoplasmic transport and the exchange of information. Gene regulation is a key component of biological activity regulation in the cell. Transcription factors control the expression levels of various genes that are necessary for the maintenance or conversion of cellular states during animal development. Because transcription factor activities determine the extent of transcription of target genes, the number of active transcription factors must be tightly regulated...
February 2, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28148649/c3g-shows-regulated-nucleo-cytoplasmic-exchange-and-represses-histone-modifications-associated-with-euchromatin
#20
Dhruv Kumar Shakyawar, Kunal Dayma, Anesh Ramadhas, Chavvakula Varalakshmi, Vegesna Radha
C3G (RapGEF1) is a ubiquitously expressed guanine nucleotide exchange factor that functions in signaling pathways regulating cell proliferation, apoptosis, and actin reorganization. It is essential for differentiation, and early embryonic development in mice. Over-expressed C3G shows predominant cytoplasmic localization, but endogenous C3G is a component of nuclear fractions in a variety of cell types. Co-expression of Importin-α and inhibition of nuclear export by Leptomycin B resulted in predominant nuclear localization of C3G...
February 1, 2017: Molecular Biology of the Cell
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