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Cap-dependent translation

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https://www.readbyqxmd.com/read/29116477/4egi-1-represses-cap-dependent-translation-and-regulates-genome-wide-translation-in-malignant-pleural-mesothelioma
#1
Arpita De, Blake A Jacobson, Mark S Peterson, Joe Jay-Dixon, Marian G Kratzke, Ahad A Sadiq, Manish R Patel, Robert A Kratzke
Deregulation of cap-dependent translation has been implicated in the malignant transformation of numerous human tissues. 4EGI-1, a novel small-molecule inhibitor of cap-dependent translation, disrupts formation of the eukaryotic initiation factor 4F (eIF4F) complex. The effects of 4EGI-1-mediated inhibition of translation initiation in malignant pleural mesothelioma (MPM) were examined. 4EGI-1 preferentially inhibited cell viability and induced apoptosis in MPM cells compared to normal mesothelial (LP9) cells...
November 8, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29112379/high-throughput-chemical-probing-of-full-length-protein-protein-interactions
#2
James M Song, Arya Menon, Dylan C Mitchell, Oleta T Johnson, Amanda L Garner
Human biology is regulated by a complex network of protein-protein interactions (PPIs), and disruption of this network has been implicated in many diseases. However, the targeting of PPIs remains a challenging area for chemical probe and drug discovery. Although many methodologies have been put forth to facilitate these efforts, new technologies are still needed. Current biochemical assays for PPIs are typically limited to motif-domain and domain-domain interactions, and assays that will enable the screening of full-length protein systems, which are more biologically relevant, are sparse...
November 14, 2017: ACS Combinatorial Science
https://www.readbyqxmd.com/read/29107537/base-resolution-mapping-reveals-distinct-m-1-a-methylome-in-nuclear-and-mitochondrial-encoded-transcripts
#3
Xiaoyu Li, Xushen Xiong, Meiling Zhang, Kun Wang, Ying Chen, Jun Zhou, Yuanhui Mao, Jia Lv, Danyang Yi, Xiao-Wei Chen, Chu Wang, Shu-Bing Qian, Chengqi Yi
Gene expression can be post-transcriptionally regulated via dynamic and reversible RNA modifications. N(1)-methyladenosine (m(1)A) is a recently identified mRNA modification; however, little is known about its precise location and biogenesis. Here, we develop a base-resolution m(1)A profiling method, based on m(1)A-induced misincorporation during reverse transcription, and report distinct classes of m(1)A methylome in the human transcriptome. m(1)A in 5' UTR, particularly those at the mRNA cap, associate with increased translation efficiency...
October 25, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29107534/m-6-a-facilitates-eif4f-independent-mrna-translation
#4
Ryan A Coots, Xiao-Min Liu, Yuanhui Mao, Leiming Dong, Jun Zhou, Ji Wan, Xingqian Zhang, Shu-Bing Qian
In eukaryotic cells, protein synthesis typically begins with the binding of eIF4F to the 7-methylguanylate (m(7)G) cap found on the 5' end of the majority of mRNAs. Surprisingly, overall translational output remains robust under eIF4F inhibition. The broad spectrum of eIF4F-resistant translatomes is incompatible with cap-independent translation mediated by internal ribosome entry sites (IRESs). Here, we report that N(6)-methyladenosine (m(6)A) facilitates mRNA translation that is resistant to eIF4F inactivation...
October 23, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29107182/identification-of-the-internal-ribosome-entry-sites-ires-of-prion-protein-gene
#5
Xiao-Nuan Luo, Qin-Qin Song, Jie Yu, Juan Song, Xin-Ling Wang, Dong Xia, Peng Sun, Jun Han
Many studies demonstrated that there are several type bands of prion protein in cells. However, the formation of different prion protein bands is elusive. After several low molecular weight bands of prion protein appeared in SMB-S15 cells infected with scrapie agent Chandler, we think that IRES-dependent translation mechanism induced by prion is involved in the formation of prion protein bands. Then we designed a series of pPrP-GFP fusing plasmids and bicistronic plasmids to identify the IRES sites of prion protein gene and found 3 IRES sites inside of PrP mRNA...
October 26, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29093101/vp1-and-vp3-are-required-and-sufficient-for-translation-initiation-of-uncapped-ibdv-genomic-dsrna
#6
Chengjin Ye, Yu Wang, Enli Zhang, Xinpeng Han, Zhaoli Yu, Hebin Liu
Infectious bursal disease virus (IBDV) is a bi-segmented double-strand RNA (dsRNA) virus of the Birnaviridae family. While IBDV genomic dsRNA lacks a 5' cap, the means by which the uncapped IBDV genomic RNA is translated effectively is unknown. In this study, we describe a cap-independent pathway of translation initiation of IBDV uncapped RNA that relies on VP1 and VP3. We show that neither purified IBDV genomic dsRNA nor the uncapped viral plus-sense RNA transcripts was directly translated and rescued into infectious viruses in host cells...
November 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29028794/condensin-ii-and-gait-complexes-cooperate-to-restrict-line-1-retrotransposition-in-epithelial-cells
#7
Jacqueline R Ward, Kommireddy Vasu, Emily Deutschman, Dalia Halawani, Peter A Larson, Dongmei Zhang, Belinda Willard, Paul L Fox, John V Moran, Michelle S Longworth
LINE-1 (L1) retrotransposons can mobilize (retrotranspose) within the human genome, and mutagenic de novo L1 insertions can lead to human diseases, including cancers. As a result, cells are actively engaged in preventing L1 retrotransposition. This work reveals that the human Condensin II complex restricts L1 retrotransposition in both non-transformed and transformed cell lines through inhibition of L1 transcription and translation. Condensin II subunits, CAP-D3 and CAP-H2, interact with members of the Gamma-Interferon Activated Inhibitor of Translation (GAIT) complex including the glutamyl-prolyl-tRNA synthetase (EPRS), the ribosomal protein L13a, Glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and NS1 associated protein 1 (NSAP1)...
October 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28982715/capturing-the-asc1p-rack1-microenvironment-at-the-head-region-of-the-40s-ribosome-with-quantitative-bioid-in-yeast
#8
Nadine Opitz, Kerstin Schmitt, Verena Hofer-Pretz, Bettina Neumann, Heike Krebber, Gerhard H Braus, Oliver Valerius
The Asc1 protein of Saccharomyces cerevisiae is a scaffold protein at the head region of ribosomal 40S that links mRNA translation to cellular signaling. In this study, proteins that co-localize with Asc1p were identified with proximity-dependent Biotin IDentification (BioID), an in vivo labeling technique described here for the first time for yeast. Biotinylated Asc1p-birA*-proximal proteins were identified and quantitatively verified against controls applying SILAC and mass spectrometry. The mRNA-binding proteins Sro9p and Gis2p appeared together with Scp160p, each providing ribosomes with nuclear transcripts...
October 5, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28981715/rna-guanine-7-methyltransferase-catalyzes-the-methylation-of-cytoplasmically-recapped-rnas
#9
Jackson B Trotman, Andrew J Giltmier, Chandrama Mukherjee, Daniel R Schoenberg
Cap homeostasis is a cyclical process of decapping and recapping that impacts a portion of the mRNA transcriptome. The metastable uncapped forms of recapping targets redistribute from polysomes to non-translating mRNPs, and recapping is all that is needed for their return to the translating pool. Previous work identified a cytoplasmic capping metabolon consisting of capping enzyme (CE) and a 5'-monophosphate kinase bound to adjacent domains of Nck1. The current study identifies the canonical cap methyltransferase (RNMT) as the enzyme responsible for guanine-N7 methylation of recapped mRNAs...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28978144/targeting-the-pi3k-akt-mtor-signaling-pathway-as-an-effectively-radiosensitizing-strategy-for-treating-human-oral-squamous-cell-carcinoma-in-vitro-and-in-vivo
#10
Chih-Chia Yu, Shih-Kai Hung, Hon-Yi Lin, Wen-Yen Chiou, Moon-Sing Lee, Hui-Fen Liao, Hsien-Bin Huang, Hsu-Chueh Ho, Yu-Chieh Su
Radiation therapy (RT) is the current standard adjuvant approach for oral squamous cell carcinoma (OSCC) patients. Radioresistance is a major contributor to radiotherapy failure. In this study, we used patient-derived cells and a radiation-resistant cell line in vitro and in vivo for two purposes: evaluate the anti-tumor effects and understand the mechanisms in the dual PI3K/mTOR signaling pathway regulation of radiosensitization. Our findings indicate that in OML1-R cells, the radioresistance phenotype is associated with activation of the PI3K/AKT/mTOR signaling pathway...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28971629/regulation-and-function-of-cmtr1-dependent-mrna-cap-methylation
#11
REVIEW
Francisco Inesta-Vaquera, Victoria H Cowling
mRNA is modified co-transcriptionally at the 5' end by the addition of an inverted guanosine cap structure which can be methylated at several positions. The mRNA cap recruits proteins involved in gene expression and identifies the transcript as being cellular or 'self' in the innate immune response. Methylation of the first transcribed nucleotide on the ribose 2'-O position is a prevalent cap modification which has roles in splicing, translation and provides protection against the innate immune response. In this review, we discuss the regulation and function of CMTR1, the first transcribed nucleotide ribose 2'-O methyltransferase, and the molecular interactions which mediate methylated 2'-O ribose function...
October 2, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28971096/protein-translation-and-signaling-in-human-eosinophils
#12
REVIEW
Stephane Esnault, Zhong-Jian Shen, James S Malter
We have recently reported that, unlike IL-5 and GM-CSF, IL-3 induces increased translation of a subset of mRNAs. In addition, we have demonstrated that Pin1 controls the activity of mRNA binding proteins, leading to enhanced mRNA stability, GM-CSF protein production and prolonged eosinophil (EOS) survival. In this review, discussion will include an overview of cap-dependent protein translation and its regulation by intracellular signaling pathways. We will address the more general process of mRNA post-transcriptional regulation, especially regarding mRNA binding proteins, which are critical effectors of protein translation...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28968974/cap-dependent-translational-control-of-oncolytic-measles-virus-infection-in-malignant-mesothelioma
#13
Blake A Jacobson, Ahad A Sadiq, Shaogeng Tang, Joe Jay-Dixon, Manish R Patel, Jeremy Drees, Brent S Sorenson, Stephen J Russell, Robert A Kratzke
Malignant mesothelioma has a poor prognosis for which there remains an urgent need for successful treatment approaches. Infection with the Edmonston vaccine strain (MV-Edm) derivative of measles virus results in lysis of cancer cells and has been tested in clinical trials for numerous tumor types including mesothelioma. Many factors play a role in MV-Edm tumor cell selectivity and cytopathic activity while also sparing non-cancerous cells. The MV-Edm receptor CD46 (cluster of differentiation 46) was demonstrated to be significantly higher in mesothelioma cells than in control cells...
September 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28949448/vcp-inhibitors-induce-endoplasmic-reticulum-stress-cause%C3%A2-cell-cycle-arrest-trigger-caspase-mediated-cell-death%C3%A2-and-synergistically-kill-ovarian-cancer-cells-in-combination-with-salubrinal
#14
(no author information available yet)
Valosin-containing protein (VCP) or p97, a member of AAA-ATPase protein family, has been associated with various cellular functions including endoplasmic reticulum-associated degradation (ERAD), Golgi membrane reassembly, autophagy, DNA repair, and cell division. Recent studies identified VCP and ubiquitin proteasome system (UPS) as synthetic lethal targets in ovarian cancer. Here, we describe the preclinical activity of VCP inhibitors in ovarian cancer. Results from our studies suggest that quinazoline-based VCP inhibitors initiate G1 cell cycle arrest, attenuate cap-dependent translation and induce programmed cell death via the intrinsic and the extrinsic modes of apoptosis...
December 2016: Molecular Oncology
https://www.readbyqxmd.com/read/28934492/concerted-action-of-two-3-cap-independent-translation-enhancers-increases-the-competitive-strength-of-translated-viral-genomes
#15
Zhiyou Du, Olga M Alekhina, Konstantin S Vassilenko, Anne E Simon
Several families of plant viruses evolved cap-independent translation enhancers (3'CITE) in the 3' untranslated regions of their genomic (g)RNAs to compete with ongoing cap-dependent translation of cellular mRNAs. Umbravirus Pea enation mosaic virus (PEMV)2 is the only example where three 3'CITEs enhance translation: the eIF4E-binding Panicum mosaic virus-like translational enhancer (PTE) and ribosome-binding 3' T-shaped structure (TSS) have been found in viruses of different genera, while the ribosome-binding kl-TSS that provides a long-distance interaction with the 5' end is unique...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28931068/erk1-2-signalling-protects-against-apoptosis-following-endoplasmic-reticulum-stress-but-cannot-provide-long-term-protection-against-bax-bak-independent-cell-death
#16
Nicola J Darling, Kathryn Balmanno, Simon J Cook
Disruption of protein folding in the endoplasmic reticulum (ER) causes ER stress. Activation of the unfolded protein response (UPR) acts to restore protein homeostasis or, if ER stress is severe or persistent, drive apoptosis, which is thought to proceed through the cell intrinsic, mitochondrial pathway. Indeed, cells that lack the key executioner proteins BAX and BAK are protected from ER stress-induced apoptosis. Here we show that chronic ER stress causes the progressive inhibition of the extracellular signal-regulated kinase (ERK1/2) signalling pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28930151/perk-signal-modulated-protein-translation-promotes-the-survivability-of-dengue-2-virus-infected-mosquito-cells-and-extends-viral-replication
#17
Jiun-Nan Hou, Tien-Huang Chen, Yi-Hsuan Chiang, Jing-Yun Peng, Tsong-Han Yang, Chih-Chieh Cheng, Eny Sofiyatun, Cheng-Hsun Chiu, Chuan Chiang-Ni, Wei-June Chen
Survival of mosquitoes from dengue virus (DENV) infection is a prerequisite of viral transmission to the host. This study aimed to see how mosquito cells can survive the infection during prosperous replication of the virus. In C6/36 cells, global protein translation was shut down after infection by DENV type 2 (DENV2). However, it returned to a normal level when infected cells were treated with an inhibitor of the protein kinase RNA (PKR)-like ER kinase (PERK) signaling pathway. Based on a 7-Methylguanosine 5'-triphosphate (m7GTP) pull-down assay, the eukaryotic translation initiation factor 4F (eIF4F) complex was also identified in DENV2-infected cells...
September 20, 2017: Viruses
https://www.readbyqxmd.com/read/28922394/sequence-features-of-viral-and-human-internal-ribosome-entry-sites-predictive-of-their-activity
#18
Alexey A Gritsenko, Shira Weingarten-Gabbay, Shani Elias-Kirma, Ronit Nir, Dick de Ridder, Eran Segal
Translation of mRNAs through Internal Ribosome Entry Sites (IRESs) has emerged as a prominent mechanism of cellular and viral initiation. It supports cap-independent translation of select cellular genes under normal conditions, and in conditions when cap-dependent translation is inhibited. IRES structure and sequence are believed to be involved in this process. However due to the small number of IRESs known, there have been no systematic investigations of the determinants of IRES activity. With the recent discovery of thousands of novel IRESs in human and viruses, the next challenge is to decipher the sequence determinants of IRES activity...
September 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28904350/tia1-dependent-regulation-of-mrna-subcellular-location-and-translation-controls-p53-expression-in-b-cells
#19
Manuel D Díaz-Muñoz, Vladimir Yu Kiselev, Nicolas Le Novère, Tomaz Curk, Jernej Ule, Martin Turner
Post-transcriptional regulation of cellular mRNA is essential for protein synthesis. Here we describe the importance of mRNA translational repression and mRNA subcellular location for protein expression during B lymphocyte activation and the DNA damage response. Cytoplasmic RNA granules are formed upon cell activation with mitogens, including stress granules that contain the RNA binding protein Tia1. Tia1 binds to a subset of transcripts involved in cell stress, including p53 mRNA, and controls translational silencing and RNA granule localization...
September 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/28858511/anchimerically-activated-protides-as-inhibitors-of-cap-dependent-translation-and-inducers-of-chemosensitization-in-mantle-cell-lymphoma
#20
Aniekan Okon, JingJing Han, Surendra Dawadi, Christos Demosthenous, Courtney C Aldrich, Mamta Gupta, Carston R Wagner
The cellular delivery of nucleotides through various pronucleotide strategies has expanded the utility of nucleosides as a therapeutic class. Although highly successful, the highly popular ProTide system relies on a four-step enzymatic and chemical process to liberate the corresponding monophosphate. To broaden the scope and reduce the number of steps required for monophosphate release, we have developed a strategy that depends on initial chemical activation by a sulfur atom of a methylthioalkyl protecting group, followed by enzymatic hydrolysis of the resulting phosphoramidate monoester...
October 12, 2017: Journal of Medicinal Chemistry
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