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Cap-dependent translation

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https://www.readbyqxmd.com/read/28613837/artificial-off-riboswitches-that-downregulate-internal-ribosome-entry-without-hybridization-switches-in-a-eukaryotic-cell-free-translation-system
#1
Atsushi Ogawa, Hiroki Masuoka, Tsubasa Ota
We constructed novel artificial riboswitches that function in a eukaryotic translation system (wheat germ extract), by rationally implanting an in vitro-selected aptamer into the intergenic internal ribosome entry site (IRES) of Plautia stali intestine virus. These eukaryotic OFF-riboswitches (OFF-eRSs) ligand-dose-dependently downregulate IRES-mediated translation without hybridization switches, which typical riboswitches utilize for gene regulation. The hybridization-switch-free mechanism not only allows for easy design but also requires less energy for regulation, resulting in a higher switching efficiency than hybridization-switch-based OFF-eRSs provide...
June 14, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28599981/p90rsk-blockade-inhibits-dual-braf-and-mek-inhibitor-resistant-melanoma-by-targeting-protein-synthesis
#2
Nicholas Theodosakis, Goran Micevic, Casey G Langdon, Alessandra Ventura, Robert Means, David F Stern, Marcus W Bosenberg
Despite improvements in survival in metastatic melanoma with combined BRAF and MEK inhibitor treatment, the overwhelming majority of patients eventually acquire resistance to both agents. Consequently, new targets for therapy in resistant tumors are currently being evaluated. Previous studies have identified p90RSK family kinases as key factors for growth and proliferation, as well as protein synthesis via assembly of the m(7)-GTP cap-dependent translation complex. We sought to evaluate inhibitors of p90RSK family members: BI-D1870 and BRD7389, for their ability to inhibit both proliferation and protein synthesis in patient-derived melanoma cell lines with acquired resistance to combined treatment with the BRAF inhibitor vemurafenib and MEK inhibitor selumetinib...
June 6, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28584194/efficient-and-accurate-translation-initiation-directed-by-tisu-involves-rps3-and-rps10e-binding-and-differential-eif1a-regulation
#3
Ora Haimov, Hadar Sinvani, Franck Martin, Igor Ulitsky, Rafi Emmanuel, Ana Tamarkin-Ben-Harush, Assaf Vardy, Rivka Dikstein
Canonical translation initiation involves ribosomal scanning but short 5' UTR mRNAs are translated in a scanning-independent manner. The extent and mechanism of scanning independent translation is not fully understood. Here we report that short 5' UTR mRNAs constitute a substantial fraction of the translatome. Short 5' UTR mRNAs are enriched with TISU, a 12-nucleotide element directing efficient scanning-independent translation. Comprehensive mutagenesis revealed that each AUG flanking nucleotides of TISU contributes to translational strength but only few are important for accuracy...
June 5, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28577281/acquired-tamoxifen-resistance-in-mcf-7-breast-cancer-cells-requires-hyperactivation-of-eif4f-mediated-translation
#4
Dedra H Fagan, Lynsey M Fettig, Svetlana Avdulov, Heather Beckwith, Mark S Peterson, Yen-Yi Ho, Fan Wang, Vitaly A Polunovsky, Douglas Yee
While selective estrogen receptor modulators, such as tamoxifen, have contributed to increased survival in patients with hormone receptor-positive breast cancer, the development of resistance to these therapies has led to the need to investigate other targetable pathways involved in oncogenic signaling. Approval of the mTOR inhibitor everolimus in the therapy of secondary endocrine resistance demonstrates the validity of this approach. Importantly, mTOR activation regulates eukaryotic messenger RNA translation...
June 2, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28559344/viral-and-cellular-mrna-specific-activators-harness-pabp-and-eif4g-to-promote-translation-initiation-downstream-of-cap-binding
#5
Richard W P Smith, Ross C Anderson, Osmany Larralde, Joel W S Smith, Barbara Gorgoni, William A Richardson, Poonam Malik, Sheila V Graham, Nicola K Gray
Regulation of mRNA translation is a major control point for gene expression and is critical for life. Of central importance is the complex between cap-bound eukaryotic initiation factor 4E (eIF4E), eIF4G, and poly(A) tail-binding protein (PABP) that circularizes mRNAs, promoting translation and stability. This complex is often targeted to regulate overall translation rates, and also by mRNA-specific translational repressors. However, the mechanisms of mRNA-specific translational activation by RNA-binding proteins remain poorly understood...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28559306/a-helicase-independent-activity-of-eif4a-in-promoting-mrna-recruitment-to-the-human-ribosome
#6
Masaaki Sokabe, Christopher S Fraser
In the scanning model of translation initiation, the decoding site and latch of the 40S subunit must open to allow the recruitment and migration of messenger RNA (mRNA); however, the precise molecular details for how initiation factors regulate mRNA accommodation into the decoding site have not yet been elucidated. Eukaryotic initiation factor (eIF) 3j is a subunit of eIF3 that binds to the mRNA entry channel and A-site of the 40S subunit. Previous studies have shown that a reduced affinity of eIF3j for the 43S preinitiation complex (PIC) occurs on eIF4F-dependent mRNA recruitment...
May 30, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28557706/downregulation-of-p68-rna-helicase-ddx5-activates-a-survival-pathway-involving-mtor-and-mdm2-signals
#7
M Kokolo, M Bach-Elias
The DEAD box p68 RNA helicase (DDX5) is required to manipulate RNA structures implicated in mRNA/rRNA processing and transcript export, and acts as a co-activator for a range of transcription factors. Previous research has indicated that p68 RNA helicase may also be important in tumour development. Wild-type HeLa and stable HeLa (clone 13) cell cultures containing RNAi-mediated depletion of p68 RNA helicase induced by doxycycline (DOX) were used to study how the p68 RNA helicase affects the mTOR cell signalling pathway...
2017: Folia Biologica (Praha)
https://www.readbyqxmd.com/read/28555065/a-novel-micro-cold-atmospheric-plasma-device-for-glioblastoma-both-in-vitro-and-in-vivo
#8
Zhitong Chen, Hayk Simonyan, Xiaoqian Cheng, Eda Gjika, Li Lin, Jerome Canady, Jonathan H Sherman, Colin Young, Michael Keidar
Cold atmospheric plasma (CAP) treatment is a rapidly expanding and emerging technology for cancer treatment. Direct CAP jet irradiation is limited to the skin and it can also be invoked as a supplement therapy during surgery as it only causes cell death in the upper three to five cell layers. However, the current cannulas from which the plasma emanates are too large for intracranial applications. To enhance efficiency and expand the applicability of the CAP method for brain tumors and reduce the gas flow rate and size of the plasma jet, a novel micro-sized CAP device (µCAP) was developed and employed to target glioblastoma tumors in the murine brain...
May 30, 2017: Cancers
https://www.readbyqxmd.com/read/28548627/combined-single-molecule-experimental-and-computational-approaches-for-understanding-the-unfolding-pathway-of-a-viral-translation-enhancer-that-participates-in-a-conformational-switch
#9
My-Tra Le, Wojciech K Kasprzak, Bruce A Shapiro, Anne E Simon
How plus-strand [+]RNA virus genomes transition from translation templates to replication templates is a matter of much speculation. We have previously proposed that, for Turnip crinkle virus, binding of the encoded RNA-dependent RNA polymerase (RdRp) to the 3'UTR of the [+]RNA template promotes a regional wide-spread conformational switch to an alternative structure that disassembles the cap-independent translation element (CITE) in the 3'UTR. The active 3'CITE folds into a tRNA-like T-shaped structure (TSS) that binds to 80S ribosomes and 60S subunits in the P-site...
May 26, 2017: RNA Biology
https://www.readbyqxmd.com/read/28539821/stabilization-of-4e-bp1-by-pi3k-kinase-and-its-involvement-in-chk2-phosphorylation-in-the-cellular-response-to-radiation
#10
Zi-Jian Yu, Hui-Hui Luo, Zeng-Fu Shang, Hua Guan, Bei-Bei Xiao, Xiao-Dan Liu, Yu Wang, Bo Huang, Ping-Kun Zhou
Objectives: 4E-BP1 is a family member of eIF4E binding proteins (4E-BPs) which act as the suppressors of cap-dependent translation of RNA via competitively associating with cap-bound eIF4E. RNA translation regulation is an important manner to control the cellular responses to a series of stress conditions such as ionizing radiation (IR)-induced DNA damage response and cell cycle controlling. This study aimed to determine the mechanism of 4E-BP1 stabilization and its potential downstream target(s) in the response to IR...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28539447/a-map-of-the-arenavirus-nucleoprotein-host-protein-interactome-reveals-that-jun%C3%A3-n-virus-selectively-impairs-the-antiviral-activity-of-pkr
#11
Benjamin R King, Dylan Hershkowitz, Philip L Eisenhauer, Marion E Weir, Christopher M Ziegler, Joanne Russo, Emily A Bruce, Bryan A Ballif, Jason Botten
Arenaviruses are enveloped negative-strand RNA viruses that cause significant human disease. Encoding only four proteins to accomplish the viral life cycle, each arenavirus protein likely plays unappreciated accessory roles during infection. Here, we used immunoprecipitation and mass spectrometry to identify human proteins that interact with the nucleoprotein (NP) of the Old World arenavirus lymphocytic choriomeningitis (LCMV) and the New World arenavirus Junín Candid #1 (JUNV). Bioinformatic analysis of the identified protein partners of NP revealed that host translation appears to be a key biological process engaged during infection...
May 24, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28537239/-translational-efficiency-of-bvdv-ires-and-emcv-ires-for-t7-rna-polymerase-driven-cytoplasmic-expression-in-mammalian-cell-lines
#12
F Ghassemi, O Madadgar, F Roohvand, M Rasekhian, M H Etemadzadeh, G R N Boroujeni, A G Langroudi, K Azadmanesh
Mammalian T7 polymerase-based cytoplasmic expression systems are common tool for molecular studies. The majority of these systems include the internal ribosome entry site (IRES) of the encephalomyocarditis virus (EMCV). To carry out a cap-independent translation process, this type of IRES might require the expression of an extensive array of host factors, what is a disadvantage. Other IRESes might be less dependent on the host cell factors, but their biology is characterized to a lesser degree. Here, we compare the translational efficiencies of bovine viral diarrhea virus (BVDV) IRES with that of ECMV...
March 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28533436/metformin-synergizes-with-bcl-xl-bcl-2-inhibitor-abt-263-to-induce-apoptosis-specifically-in-p53-defective-cancer-cells
#13
Xinzhe Li, Bo Li, Zhenhong Ni, Peng Zhou, Bin Wang, Jintao He, Haojun Xiong, Fan Yang, Yaran Wu, Xilin Lyu, Yan Zhang, Yijun Zeng, Jiqin Lian, Fengtian He
p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the pro-apoptotic machineries in various p53-defective cancer cells...
May 22, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28529622/ires-mediated-protein-translation-overcomes-suppression-by-the-p14arf-tumor-suppressor-protein
#14
Song Xi, Ming Zhao, Si Wang, Ling Ma, Shensen Wang, Xianling Cong, Ruth A Gjerset, Rebecca C Fitzgerald, Yinghui Huang
Internal ribosome entry sites (IRES elements) have attracted interest in cancer gene therapy because they can be used in the design of gene transfer vectors that provide bicistronic co-expression of two transgene products under the control of a single promoter. Unlike cellular translation of most mRNAs, a process that requires a post-translational 5' modification of the mRNA known as the cap structure, IRES-mediated translation is independent of the cap structure. The cellular conditions that may intervene to modulate IRES-mediated, cap-independent versus cap-dependent translation, however, remain poorly understood, although they could be critical to the choice of gene transfer vectors...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28518150/cycloheximide-promotes-paraptosis-induced-by-inhibition-of-cyclophilins-in-glioblastoma-multiforme
#15
Lin Wang, Justin H Gundelach, Richard J Bram
Cancer is the second leading cause of death worldwide. Current treatment strategies based on multi-agent chemotherapy and/or radiation regimens have improved overall survival in some cases. However, resistance to apoptosis often develops in cancer cells, and its occurrence is thought to contribute to treatment failure. Non-apoptotic cell death mechanisms have become of great interest, therefore, in hopes that they would bypass tumor cell resistance. Glioblastoma multiforme (GBM), a grade IV astrocytic tumor is the most frequent brain tumor in adults, and has a high rate of mortality...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28507282/p53-suppresses-ribonucleotide-reductase-via-inhibiting-mtorc1
#16
Zhengfu He, Xing Hu, Weijin Liu, Adrienne Dorrance, Ramiro Garzon, Peter J Houghton, Changxian Shen
Balanced deoxyribonucleotides pools are essential for cell survival and genome stability. Ribonucleotide reductase is the rate-limiting enzyme for the production of deoxyribonucleotides. We report here that p53 suppresses ribonucleotide reductase subunit 1 (RRM1) and 2 (RRM2) via inhibiting mammalian target of rapamycin complex 1 (mTORC1). In vitro, cancer cell lines and mouse embryonic fibroblast cells were treated with different concentrations of pharmacological inhibitors for different times. In vivo, rhabdomyosarcoma Rh30 cell tumor-bearing mice were treated with rapamycin or AZD8055...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28468879/regulation-of-tacaribe-mammarenavirus-translation-positive-5-and-negative-3-elements-and-role-of-key-cellular-factors
#17
Sabrina Foscaldi, Alejandra D'Antuono, María Gabriela Noval, Gonzalo de Prat Gay, Luis Scolaro, Nora Lopez
Mammarenaviruses are enveloped viruses with a bisegmented negative-stranded RNA genome that encodes the nucleocapsid protein (NP), the envelope glycoprotein precursor (GPC), the RNA polymerase (L), and a RING matrix protein (Z). Viral proteins are synthesized from subgenomic messenger RNAs bearing a capped 5' untranslated region (UTR), and lacking 3' poly(A) tail. We analyzed the translation strategy of Tacaribe virus (TCRV), a prototype of the New World mammarenaviruses. A virus-like transcript that carries a reporter gene in place of the NP open-reading frame as well as transcripts bearing modified 5' and/or 3' UTRs were evaluated in a cell-based translation assay...
May 3, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28452293/separation-of-foot-and-mouth-disease-virus-leader-protein-activities-identification-of-mutants-that-retain-efficient-self-processing-activity-but-poorly-induce-eif4g-cleavage
#18
Su Hua Guan, Graham J Belsham
Foot-and-mouth disease virus is a picornavirus and its RNA genome encodes a large polyprotein. The N-terminal part of this polyprotein is the leader protein, a cysteine protease, termed Lpro. The virus causes the rapid inhibition of host cell cap-dependent protein synthesis within infected cells. This results from the Lpro-dependent cleavage of the cellular translation initiation factor eIF4G. Lpro also releases itself from the virus capsid precursor by cleaving the L/P1 junction. Using site-directed mutagenesis of the Lpro coding sequence, we have investigated the role of 51 separate amino acid residues in the functions of this protein...
April 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28438065/reduced-expression-of-eukaryotic-translation-initiation-factor-3-subunit-e-and-its-possible-involvement-in-the-epithelial-mesenchymal-transition-in-endometriosis
#19
Xianjun Cai, Minhong Shen, Xishi Liu, Sun-Wei Guo
Epithelial-mesenchymal transition (EMT) is now well documented to be involved in the development of endometriosis through the promotion of invasion and fibrogenesis. To date, several factors have been reported to be involved in EMT in endometriosis. The eukaryotic translation initiation factor 3 subunit e (eIF3e) protein is a component of the multisubunit eIF3 complex essential for cap-dependent translation initiation. The aim of this study was to investigate whether eIF3e is involved in EMT in endometriosis...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28428795/non-canonical-translation-in-plant-rna-viruses
#20
REVIEW
Manuel Miras, W Allen Miller, Verónica Truniger, Miguel A Aranda
Viral protein synthesis is completely dependent upon the host cell's translational machinery. Canonical translation of host mRNAs depends on structural elements such as the 5' cap structure and/or the 3' poly(A) tail of the mRNAs. Although many viral mRNAs are devoid of one or both of these structures, they can still translate efficiently using non-canonical mechanisms. Here, we review the tools utilized by positive-sense single-stranded (+ss) RNA plant viruses to initiate non-canonical translation, focusing on cis-acting sequences present in viral mRNAs...
2017: Frontiers in Plant Science
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