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https://www.readbyqxmd.com/read/29454068/o-glcnacylation-of-rack1-promotes-hepatocellular-carcinogenesis
#1
Fangfang Duan, Hao Wu, Dongwei Jia, Weicheng Wu, Shifang Ren, Lan Wang, Shushu Song, Xinying Guo, Fenglin Liu, Yuanyuan Ruan, Jianxin Gu
BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis. Nevertheless, whether and how these two pathways are interlinked remain unknown. Our previous study indicated that ribosomal RACK1 promoted the chemoresistance and growth in hepatocellular carcinoma (HCC). The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis...
February 14, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29453322/the-mtor-targets-4e-bp1-2-restrain-tumor-growth-and-promote-hypoxia-tolerance-in-pten-driven-prostate-cancer
#2
Mei Ding, Theodorus H van der Kwast, Ravi N Vellanki, Warren D Foltz, Trevor D McKee, Nahum Sonenberg, Pier Paolo Pandolfi, Marianne Koritzinsky, Bradly G Wouters
The mTOR signaling pathway is a central regulator of protein synthesis and cellular metabolism in response to the availability of energy, nutrients, oxygen, and growth factors. mTOR activation leads to phosphorylation of multiple downstream targets including the eukaryotic initiation factor 4E (eIF4E) binding proteins-1 and -2 (EIF4EBP1/4E-BP1 and EIF4EBP2/4E-BP2). These binding proteins inhibit protein synthesis, but are inactivated by mTOR to stimulate cell growth and metabolism. However, the role of these proteins in the context of aberrant activation of mTOR, which occurs frequently in cancers through loss of PTEN or mutational activation of the PI3K/AKT pathway, is unclear...
February 16, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29396141/structure-and-functions-of-the-translation-initiation-factor-eif4e-and-its-role-in-cancer-development-and-treatment
#3
REVIEW
Arianna Piserà, Adele Campo, Salvatore Campo
In eukaryotic cells, protein synthesis is a complex and multi-step process that has several mechanisms to start the translation including cap-dependent and cap-independent initiation. The translation control of eukaryotic gene expression occurs principally at the initiation step. In this context, it is critical that the eukaryotic translation initiation factor eIF4E bind to the 7-methylguanosine (m7G) cap present at the 5'-UTRs of most eukaryotic mRNAs. Combined with other initiation factors, eIF4E mediates the mRNA recruitment on ribosomes to start the translation...
January 29, 2018: Journal of Genetics and Genomics, Yi Chuan Xue Bao
https://www.readbyqxmd.com/read/29387454/whole-genome-transcriptomic-insights-into-protective-molecular-mechanisms-in-metabolically-healthy-obese-african-americans
#4
Amadou Gaye, Ayo P Doumatey, Sharon K Davis, Charles N Rotimi, Gary H Gibbons
Several clinical guidelines have been proposed to distinguish metabolically healthy obesity (MHO) from other subgroups of obesity but the molecular mechanisms by which MHO individuals remain metabolically healthy despite having a high fat mass are yet to be elucidated. We conducted the first whole blood transcriptomic study designed to identify specific sets of genes that might shed novel insights into the molecular mechanisms that protect or delay the occurrence of obesity-related co-morbidities in MHO. The study included 29 African-American obese individuals, 8 MHO and 21 metabolically abnormal obese (MAO)...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29381712/plant-growth-and-fertility-requires-functional-interactions-between-specific-pabp-and-eif4g-gene-family-members
#5
Daniel R Gallie
The initiation of protein synthesis requires the involvement of the eukaryotic translation initiation factor (eIF) 4G to promote assembly of the factors needed to recruit a 40S ribosomal subunit to an mRNA. Although many eukaryotes express two eIF4G isoforms that are highly similar, those in plants, referred to as eIF4G and eIFiso4G, are highly divergent in size, sequence, and domain organization. Species of the Brassicaceae and the Cleomaceae also express a divergent eIFiso4G isoform, referred to as eIFiso4G2, not found elsewhere in the plant kingdom...
2018: PloS One
https://www.readbyqxmd.com/read/29374693/association-of-eif4e-and-sparc-expression-with-lymphangiogenesis-and-lymph-node-metastasis-in-hypopharyngeal-cancer
#6
Benjamin Philipp Ernst, Caja Mikstas, Timo Stöver, Roland Stauber, Sebastian Strieth
BACKGROUND/AIM: Head and neck squamous cell carcinomas (HNSCC) are characterized by aggressiveness, early recurrence and lymph node metastasis. Therefore, there is an urgent need to identify new biomarkers and drug targets. MATERIALS AND METHODS: Neck dissection specimens from 11 patients diagnosed with hypopharyngeal cancer were analyzed for their lymphatic vessel density (LVD) by lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1) immunostaining, expression of eukaryotic initiation factor 4E (eIF4E) and levels of secreted protein acidic and rich in cysteine (SPARC) using immunoblot analysis...
February 2018: Anticancer Research
https://www.readbyqxmd.com/read/29367404/loss-of-eif4e-phosphorylation-engenders-depression-like-behaviors-via-selective-mrna-translation
#7
Inês Silva Amorim, Sonal Kedia, Stella Kouloulia, Konstanze Simbriger, Ilse Gantois, Seyed Mehdi Jafarnejad, Yupeng Li, Agniete Kampaite, Tine Pooters, Nicola Romanò, Christos G Gkogkas
The MAPK/ERK (Mitogen Activated Protein Kinases/Extracellular signal-Regulated Kinases) pathway is a cardinal regulator of synaptic plasticity, learning and memory in the hippocampus. One of major endpoints of this signaling cascade is the 5' mRNA cap-binding protein eIF4E (eukaryotic Initiation Factor 4E), which is phosphorylated on Ser 209 by MNK (MAPK-interacting protein kinases) and controls mRNA translation. The precise role of phospho-eIF4E in the brain is yet to be determined. Herein, we demonstrate that ablation of eIF4E phosphorylation in male mice (4Eki mice) does not impair long-term spatial or contextual fear memory, or the late phase of long-term potentiation (L-LTP)...
January 24, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29367005/the-impaired-immune-function-and-structural-integrity-by-dietary-iron-deficiency-or-excess-in-gill-of-fish-after-infection-with-flavobacterium-columnare-regulation-of-nf-%C3%AE%C2%BAb-tor-jnk-p38mapk-nrf2-and-mlck-signalling
#8
Yan-Lin Guo, Pei Wu, Wei-Dan Jiang, Yang Liu, Sheng-Yao Kuang, Jun Jiang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou, Lin Feng
The aim of this study was to investigate the effects and potential mechanisms of dietary iron on immune function and structural integrity in gill of young grass carp (Ctenopharyngodon idella). A total of 630 grass carp (242.32 ± 0.58 g) were fed diets containing graded levels of iron at 12.15 (basal diet), 35.38, 63.47, 86.43, 111.09, 136.37 and 73.50 mg/kg for 60 days. Subsequently, a challenge test was conducted by infection with Flavobacterium columnare to investigate the effects of dietary iron on gill immune function and structural integrity in young grass carp...
January 20, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29360541/methionine-hydroxy-analogue-supplementation-modulates-gill-immunological-and-barrier-health-status-of-grass-carp-ctenopharyngodon-idella
#9
Pei Wu, Fei-Yu Pan, Lin Feng, Wei-Dan Jiang, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xiao-Qiu Zhou, Yang Liu
This study was conducted to investigate the effects of methionine hydroxy analogue (MHA) on the physical barrier and immune defence in the gill of young grass carp (Ctenopharyngodon idella). A total 630 young grass carp with an average initial weight of 259.70 ± 0.47 g were fed graded levels of MHA (0, 2.4, 4.4, 6.4, 8.5 and 10.5 g/kg diet) and one DL-methionine (DLM) group (6.4 g/kg diet) for 8 weeks. After feeding trial, 15 fish from each treatment were challenged with Flavobacterium columnare...
January 19, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29358667/rbm24-a-target-of-p53-is-necessary-for-proper-expression-of-p53-and-heart-development
#10
Min Zhang, Yanhong Zhang, Enshun Xu, Shakur Mohibi, Danielle Michelle de Anda, Yuqian Jiang, Jin Zhang, Xinbin Chen
Activation of p53-dependent apoptosis is critical for tumor suppression but aberrant activation of p53 also leads to developmental defects and heart failure. Here, we found that Rbm24 RNA-binding protein, a target of p53, regulates p53 mRNA translation. Mechanistically, we found that through binding to p53 mRNA and interaction with translation initiation factor eIF4E, Rbm24 prevents eIF4E from binding to p53 mRNA and inhibits the assembly of translation initiation complex. Importantly, we showed that mice deficient in Rbm24 die in utero due to the endocardial cushion defect in the heart at least in part due to aberrant activation of p53-dependent apoptosis...
January 22, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29352035/using-mouse-transgenic-and-human-stem-cell-technologies-to-model-genetic-mutations-associated-with-schizophrenia-and-autism
#11
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
#12
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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