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https://www.readbyqxmd.com/read/29352035/using-mouse-transgenic-and-human-stem-cell-technologies-to-model-genetic-mutations-associated-with-schizophrenia-and-autism
#1
REVIEW
David St Clair, Mandy Johnstone
Solid progress has occurred over the last decade in our understanding of the molecular genetic basis of neurodevelopmental disorders, and of schizophrenia and autism in particular. Although the genetic architecture of both disorders is far more complex than previously imagined, many key loci have at last been identified. This has allowed in vivo and in vitro technologies to be refined to model specific high-penetrant genetic loci involved in both disorders. Using the DISC1/NDE1 and CYFIP1/EIF4E loci as exemplars, we explore the opportunities and challenges of using animal models and human-induced pluripotent stem cell technologies to further understand/treat and potentially reverse the worst consequences of these debilitating disorders...
March 19, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/29342273/hypermethylation-of-eif4e-promoter-is-associated-with-early-onset-of-gastric-cancer
#2
Yuqiu Ge, Qin Wu, Gaoxiang Ma, Wei Shao, Hanting Liu, Qiang Zhang, Junyi Xin, Yao Xue, Mulong Du, Qinghong Zhao, Meilin Wang, Haiyan Chu, Zhengdong Zhang
Although gastric cancer (GC) in young adults (≤ 45 years) accounts for fewer than 10% of newly diagnosed cases, the young patients are more likely to have advanced disease at presentation compared with elderly patients. Previous studies have identified that the DNA methylation of genomes are different during aging. Our study aimed to explore the association between DNA methylation and the onset of GC. We applied Illumina HumanMethylation450 BeadChip to examine methylation expression profiles and compared methylation expression patterns in five early onset GC patients and seven elderly patients...
January 12, 2018: Carcinogenesis
https://www.readbyqxmd.com/read/29339492/cytocapsular-tubes-conduct-cell-translocation
#3
Tingfang Yi, Gerhard Wagner
Cell locomotion is essential for multicellular organism embryo development, organ homeostasis, tissue regeneration, immune responses, and tumor metastasis. Here we report that single mammalian cells can generate two extracellular membranous compartments: cytocapsulae and cytocapsular tubes. Cells migrate in cytocapsulae and engender cytocapsular tubes, which exhibit pleiotropic biological functions and provide tubular routes for directed cell transportation. Ultrastructural analysis by electron microscope revealed that nanoprotrusions surround and anchor cytocapsular tubes in place...
January 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29334312/targeting-of-phospho-eif4e-by-homoharringtonine-eradicates-a-distinct-subset-of-human-acute-myeloid-leukemia
#4
Hong Zhou, Rong Zhen Xu, Ying Gu, Peng Fei Shi, Shenxian Qian
More than half of the patients with acute myeloid leukemia (AML) fail to achieve long-term disease-free survival with current therapies and novel therapeutic strategies are urgently needed. The effects of homoharringtonine (HHT) on the growth of AML cell lines and primary leukemia cells were examined using MTT, colony formation assay. The effects of HHT on both eukaryotic translation initiation factor 4E (eIF4E) and phospho-eIF4E(p-eIF4E) were examined through western blot and immunofluorescence staining. HHT selectively reduced levels of p-eIF4E and its downstream oncoprotein Mcl-1, and potently inhibited in vitro and in vivo the growth of a distinct subset of AML cells and primary leukemia cells expressing high level of p-eIF4E through apoptosis...
January 15, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29333921/targeting-brd4-proteins-suppresses-the-growth-of-nsclc-through-downregulation-of-eif4e-expression
#5
Zhongyuan Gao, Ting Yuan, Xiao Zhou, Ping Ni, Geng Sun, Ping Li, Zhixiang Cheng, Xuerong Wang
Lung cancer is the leading cause of cancer-related death worldwide. Bromodomain and extraterminal domain (BET) proteins act as epigenome readers for gene transcriptional regulation. Among BET family members, BRD4 was well studied, but for its mechanism in non-small cell lung carcinoma has not been elucidated. eIF4E regulates gene translation and has been proved to play an important role in the progression of lung cancer. In this study, we first confirmed that BET inhibitors JQ1 and I-BET151 suppressed the growth of NSCLCs, in parallel with downregulated eIF4E expression...
January 15, 2018: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29333098/mir-22-3p-regulates-cell-proliferation-and-inhibits-cell-apoptosis-through-targeting-the-eif4ebp3-gene-in-human-cervical-squamous-carcinoma-cells
#6
Kang-Tai Lv, Zhu Liu, Jie Feng, Wei Zhao, Tao Hao, Wen-Yan Ding, Jing-Ping Chu, Ling-Juan Gao
Background: MicroRNAs (miRNAs) are non-coding small RNAs that function as negative regulators of gene expression and are involved in tumour biology. The eIF4E-binding proteins (eIF4EBPs) play essential roles in preventing translation initiation and inhibiting protein synthesis at a global or message-specific level in a variety of tumours. Methods: According to comparative miRNA profiles of clinical cervical cancer and non-cancerous cervical tissue specimens, several miRNAs were aberrantly expressed in the cervical cancer samples...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29323792/the-retinamide-vnlg-152-inhibits-ar-ar-v7-and-mnk-eif4esignaling-pathways-to-suppress-emt-and-castration-resistant-prostate-cancer-xenograft-growth
#7
Vidya P Ramamurthy, Senthilmurugan Ramalingam, Lalji K Gediya, Vincent C O Njar
VNLG-152, a lead novel retinamide (NR) shown to suppress growth and progression in genetically diverse PCa cells via inhibition of AR signaling and eIF4E translational machinery. Herein, we report therapeutic effects of VNLG-152 on castration resistant prostate cancer (CRPC) growth and metastatic phenotype in CRPC tumor xenograft model. Administration of VNLG-152 significantly and dose-dependently suppressed the growth of aggressive CWR22Rv1 tumors by 63.4% and 76.3% respectively (P = 0.001), vs. vehicle with no host toxicity...
January 11, 2018: FEBS Journal
https://www.readbyqxmd.com/read/29288414/trypanosoma-brucei-eif4e2-cap-binding-protein-binds-a-homolog-of-the-histone-mrna-stem-loop-binding-protein
#8
Eden R Freire, Danielle M N Moura, Maria J R Bezerra, Camila C Xavier, Mariana C Morais-Sobral, Ajay A Vashisht, Antonio M Rezende, James A Wohlschlegel, Nancy R Sturm, Osvaldo P de Melo Neto, David A Campbell
Trypanosomatids are parasitic protozoans characterized by several unique structural and metabolic processes that include exquisite mechanisms associated with gene expression and regulation. During the initiation of protein synthesis, for instance, mRNA selection for translation seems to be mediated by different eIF4F-like complexes, which may play a significant role in parasite adaptation to different hosts. In eukaryotes, the heterotrimeric eIF4F complex (formed by eIF4E, eIF4G, and eIF4A) mediates mRNA recognition and ribosome binding and participates in various translation regulatory events...
December 29, 2017: Current Genetics
https://www.readbyqxmd.com/read/29286143/epithelial-mesenchymal-transition-induced-by-the-cxcl9-cxcr3-axis-through-akt-activation-promotes-invasion-and-metastasis-in-tongue-squamous-cell-carcinoma
#9
Ziliang Li, Jianqi Liu, Lei Li, Shuai Shao, Jianhua Wu, Li Bian, Yongwen He
The present study aimed to assess the induction of epithelial-mesenchymal transition (EMT), invasion, and metastasis by the chemokine CXCL9/receptor CXCR3 axis in tongue squamous cell carcinoma (TSCC), unveiling the underlying mechanisms and providing new insights into the prevention and treatment of oral cancer metastasis. The expression levels of CXCL9 and CXCR3 in TSCC tissue specimens were determined by immunohistochemistry, assessing differences between samples with cervical lymph node metastasis and those without...
December 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/29247846/strategies-of-biochemical-adaptation-for-hibernation-in-a-south-american-marsupial-dromiciops-gliroides-2-control-of-the-akt-pathway-and-protein-translation-machinery
#10
Bryan E Luu, Sanoji Wijenayake, Jing Zhang, Shannon N Tessier, Julian F Quintero-Galvis, Juan Diego Gaitán-Espitia, Roberto F Nespolo, Kenneth B Storey
When faced with harsh environmental conditions, the South American marsupial, monito del monte (Dromiciops gliroides), reduces its body temperature and uses either daily torpor or multiday hibernation to survive. This study used ELISA and multiplex assays to characterize the responses to hibernation by three regulatory components of protein translation machinery [p-eIF2α(S51), p-eIF4E(S209), p-4EBP(Thr37/46)] and eight targets involved in upstream signaling control of translation [p-IGF-1R(Tyr1135/1136), PTEN(S380), p-Akt(S473), p-GSK-3α(S21), p-GSK-3β(S9), p-TSC2(S939), p-mTOR(S2448), and p70S6K(T412)]...
December 13, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29238357/structural-and-functional-diversity-of-plant-virus-3-cap-independent-translation-enhancers-3-cites
#11
REVIEW
Verónica Truniger, Manuel Miras, Miguel A Aranda
Most of the positive-strand RNA plant viruses lack the 5'-cap and/or the poly(A)-tail that act synergistically to stimulate canonical translation of cellular mRNAs. However, they have RNA elements in the 5'- or 3'-untranslated regions of their RNAs that are required for their cap-independent translation. Cap-independent translation enhancers (CITEs) have been identified in the genomic 3'-end of viruses belonging to the family Tombusviridae and the genus Luteovirus. Seven classes of 3'-CITEs have been described to date based on their different RNA structures...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/29212818/the-histone-demethylase-kdm5a-is-required-for-the-repression-of-astrocytogenesis-and-regulated-by-the-translational-machinery-in-neural-progenitor-cells
#12
Sun-Young Kong, Woosuk Kim, Ha-Rim Lee, Hyun-Jung Kim
Histone demethylases are known to play important roles in the determination of the fate of stem cells and in cancer progression. In this study, we show that the lysine 4 of histone H3 (H3K4), lysine-specific demethylase 5A (KDM5A) is essential for the repression of astrocyte differentiation in neural progenitor cells (NPCs), and its expression is regulated by translational machinery. Knockdown of KDM5A in NPCs increased astrocytogenesis, and conversely, KDM5A overexpression reduced the transcriptional activity of the Gfap promoter...
December 6, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29198077/fibroblast-like-synoviocyte-migration-is-enhanced-by-il-17-mediated-overexpression-of-l-type-amino-acid-transporter-1-lat1-via-the-mtor-4e-bp1-pathway
#13
Zhao Yu, Wang Lin, Zhang Rui, Pan Jihong
In rheumatoid arthritis (RA), activated synovial fibroblasts have the ability to invade joint cartilage, actively contributing to joint destruction in RA. The mechanisms underlying this cell migration and invasion remain unclear. Our previous results and data from the GEO profile indicate that the L-type amino acid transporter gene, LAT1, is overexpressed in the synovium of RA. To identify its potential role in RA, fibroblast-like synoviocytes (FLS) from patients with RA were used to determine the effects of suppressing the LAT1 genes using RNA interference and the LAT inhibitor, BCH...
December 2, 2017: Amino Acids
https://www.readbyqxmd.com/read/29195795/7-methylguanosine-monophosphate-analogues-with-5-1-2-3-triazoyl-moiety-synthesis-and-evaluation-as-the-inhibitors-of-cniiib-nucleotidase
#14
Mateusz Kozarski, Dorota Kubacka, Blazej A Wojtczak, Renata Kasprzyk, Marek R Baranowski, Joanna Kowalska
The hydrolysis of nucleoside 5'-monophosphates to the corresponding nucleosides and inorganic phosphate is catalysed by 5'-nucleotidases, thereby contributing to the control of endogenous nucleotide turnover and affecting the fate of exogenously delivered nucleotide- and nucleoside-derived therapeutics in cells. A recently identified nucleotidase cNIIIB shows preference towards 7-methylguanosine monophosphate (m7GMP) as a substrate, which suggests its potential involvement in mRNA degradation. However, the extent of biological functions and the significance of cNIIIB remains to be elucidated...
November 22, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29192585/yeast-eif4a-enhances-recruitment-of-mrnas-regardless-of-their-structural-complexity
#15
Paul Yourik, Colin Echeverría Aitken, Fujun Zhou, Neha Gupta, Alan G Hinnebusch, Jon R Lorsch
eIF4A is a DEAD-box RNA-dependent ATPase thought to unwind RNA secondary structure in the 5'-untranslated regions (UTRs) of mRNAs to promote their recruitment to the eukaryotic translation pre-initiation complex (PIC). We show that eIF4A's ATPase activity is markedly stimulated in the presence of the PIC, independently of eIF4E•eIF4G, but dependent on subunits i and g of the heteromeric eIF3 complex. Surprisingly, eIF4A accelerated the rate of recruitment of all mRNAs tested, regardless of their degree of structural complexity...
November 30, 2017: ELife
https://www.readbyqxmd.com/read/29166596/the-gcn2-atf4-signaling-pathway-induces-4e-bp-to-bias-translation-and-boost-antimicrobial-peptide-synthesis-in-response-to-bacterial-infection
#16
Deepika Vasudevan, Nicholas K Clark, Jessica Sam, Victoria C Cotham, Beatrix Ueberheide, Michael T Marr, Hyung Don Ryoo
Bacterial infection often leads to suppression of mRNA translation, but hosts are nonetheless able to express immune response genes through as yet unknown mechanisms. Here, we use a Drosophila model to demonstrate that antimicrobial peptide (AMP) production during infection is paradoxically stimulated by the inhibitor of cap-dependent translation, 4E-BP (eIF4E-binding protein; encoded by the Thor gene). We found that 4E-BP is induced upon infection with pathogenic bacteria by the stress-response transcription factor ATF4 and its upstream kinase, GCN2...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29158530/mrnas-containing-nmd-competent-premature-termination-codons-are-stabilized-and-translated-under-upf1-depletion
#17
Won Kyu Kim, SeongJu Yun, Yujin Kwon, Kwon Tae You, Nara Shin, Jiyoon Kim, Hoguen Kim
mRNAs containing premature termination codons (PTCs) are rapidly degraded through nonsense-mediated mRNA decay (NMD). However, some PTC-containing mRNAs evade NMD, and might generate mutant proteins responsible for various diseases, including cancers. Using PTC-containing human genomic β-globin constructs, we show that a fraction (~30%) of PTC-containing mRNAs expressed from NMD-competent PTC-containing constructs were as stable as their PTC-free counterparts in a steady state. These PTC-containing mRNAs were monosome-enriched and rarely contributed to expression of mutant proteins...
November 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29157222/comparative-proteomics-reveals-the-physiological-differences-between-winter-tender-shoots-and-spring-tender-shoots-of-a-novel-tea-camellia-sinensis-l-cultivar-evergrowing-in-winter
#18
Shengjie Liu, Jiadong Gao, Zhongjian Chen, Xiaoyan Qiao, Hualin Huang, Baiyuan Cui, Qingfeng Zhu, Zhangyan Dai, Hualing Wu, Yayan Pan, Chengwei Yang, Jun Liu
BACKGROUND: A recently discovered tea [Camellia sinensis (L.) O. Kuntze] cultivar can generate tender shoots in winter. We performed comparative proteomics to analyze the differentially accumulated proteins between winter and spring tender shoots of this clonal cultivar to reveal the physiological basis of its evergrowing character during winter. RESULTS: We extracted proteins from the winter and spring tender shoots (newly formed two leaves and a bud) of the evergrowing tea cultivar "Dongcha11" respectively...
November 20, 2017: BMC Plant Biology
https://www.readbyqxmd.com/read/29153483/crosstalks-between-translation-and-metabolism-in-cancer
#19
REVIEW
Stefano Biffo, Nicola Manfrini, Sara Ricciardi
Albeit cancer patients' heterogeneity, all tumor cells have alterations of both metabolism and translation. The simplest explanation for this common feature is that several oncogenes coordinate a translational and metabolic reprogramming that is necessary for tumor cells to thrive. Overall, at least three oncogenic pathways, namely c-Myc, RAS and PI3K-mTOR, are known to affect both translation and metabolism by stimulating glycolysis and protein synthesis. The crosstalk between metabolite production and the translational machinery is, instead, less understood...
November 15, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/29139201/defining-the-protein-complexome-of-translation-termination-factor-erf1-identification-of-four-novel-erf1-containing-complexes-that-range-from-20s-to-57s-in-size
#20
Clyde L Denis, Roy Richardson, Shiwha Park, Chongxu Zhang, Wen Xi, Thomas M Laue, Xin Wang
The eukaryotic eRF1 translation termination factor plays an important role in recognizing stop codons and initiating the end to translation. However, which exact complexes contain eRF1 and at what abundance is not clear. We have used analytical ultracentrifugation with fluorescent detection system to identify the protein complexome of eRF1 in the yeast Saccharomyces cerevisiae. In addition to eRF1 presence in translating polysomes, we found that eRF1 associated with five other macromolecular complexes: 77S, 57S, 39S, 28S, and 20S in size...
November 15, 2017: Proteins
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