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https://www.readbyqxmd.com/read/28630491/chronic-high-fat-feeding-restricts-islet-mrna-translation-initiation-independently-of-er-stress-via-dna-damage-and-p53-activation
#1
Masayuki Hatanaka, Emily Anderson-Baucum, Alexander Lakhter, Tatsuyoshi Kono, Bernhard Maier, Sarah A Tersey, Yukio Tanizawa, Carmella Evans-Molina, Raghavendra G Mirmira, Emily K Sims
Under conditions of high fat diet (HFD) consumption, glucose dyshomeostasis develops when β-cells are unable to adapt to peripheral insulin demands. Few studies have interrogated the molecular mechanisms of β-cell dysfunction at the level of mRNA translation under such conditions. We sought to address this issue through polyribosome profile analysis of islets from mice fed 16-weeks of 42% HFD. HFD-islet analysis revealed clear trends toward global reductions in mRNA translation with a significant reduction in the polyribosome/monoribosome ratio for Pdx1 mRNA...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28625872/decreased-enteritis-resistance-ability-by-dietary-low-or-excess-levels-of%C3%A2-lipids-through-impairing-the-intestinal-physical-and-immune-barriers-function-of-young-grass-carp-ctenopharyngodon-idella
#2
Lin Feng, Pei-Jun Ni, Wei-Dan Jiang, Pei Wu, Yang Liu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Xu Tang, He-Qun Shi, Xiao-Qiu Zhou
The current study explores the hypothesis that low or excess levels of lipids decrease the enteritis resistance ability through impairing the intestinal physical and immune barrier function of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp with an average initial weight of 261.41 ± 0.53 g were fed diets containing six graded levels of lipids at 5.9, 21.4, 36.0, 50.2, 66.6 and 80.1 g/kg for 8 weeks. After that, a challenge trial was conducted by injection of Aeromonas hydrophila over 2 weeks...
June 16, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28611474/p38%C3%AE-regulates-cytokine-induced-ifn%C3%AE-secretion-via-the-mnk1-eif4e-pathway-in-th1-cells
#3
María Salvador-Bernáldez, Sara B Mateus, Iván Del Barco Barrantes, Simon C Arthur, Carlos Martínez-A, Angel R Nebreda, Jesús M Salvador
The p38 mitogen-activated protein kinase (MAPK) pathway is involved in the regulation of immune and inflammatory processes. We used p38α-conditional, p38β-deficient, and p38α/β double-null mouse models to address the role of these two p38 MAPK in CD4(+) T cells, and found that p38α deficiency causes these cells to hyperproliferate. Our studies indicate that both p38α and p38β are dispensable for T helper cell type 1 (Th1) differentiation but, by controlling IFNγ and TNFα production, are critical for normal Th1 effector function...
June 14, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28610844/overexpression-of-eif4f-components-in-meningiomas-and-suppression-of-meningioma-cell-growth-by-inhibiting-translation-initiation
#4
REVIEW
Janet L Oblinger, Sarah S Burns, Jie Huang, Li Pan, Yulin Ren, Rulong Shen, A Douglas Kinghorn, D Bradley Welling, Long-Sheng Chang
Meningiomas frequently display activation of the PI3K/AKT/mTOR pathway, leading to elevated levels of phospho-4E binding proteins, which enhances protein synthesis; however, it is not known whether inhibition of protein translation is an effective treatment option for meningiomas. We found that human meningiomas expressed high levels of the three components of the eukaryotic initiation factor 4F (eIF4F) translation initiation complex, eIF4A, eIF4E, and eIF4G. The expression of eIF4A and eIF4E was important in sustaining the growth of NF2-deficient benign meningioma Ben-Men-1 cells, as shRNA-mediated knockdown of these proteins strongly reduced cell proliferation...
June 10, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28609214/the-potyvirus-particle-recruits-the-plant-translation-initiation-factor-eif4e-by-means-of-the-vpg-covalently-linked-to-the-viral-rna
#5
Geneviève Tavert-Roudet, Agnès Anne, Amandine Barra, Arnaud Chovin, Christophe Demaille, Thierry Michon
The VPg of potyviruses is a protein covalently linked to the 5' end of viral RNA. It interacts with eIF4E, a component of the cellular translation initiation complex. It has been suggested that the 5' RNA linked VPg could mimic the cellular mRNA cap, promoting synthesis of viral proteins. We report here evidences for evidence for recruitment of the plant eIF4E by Lettuce mosaic virus (LMV, potyvirus) particles via the 5' RNA linked VPg. Analysis of the viral population was performed by ELISA-based tests, either with crude extracts of LMV-infected tissues or purified viral particles...
June 13, 2017: Molecular Plant-microbe Interactions: MPMI
https://www.readbyqxmd.com/read/28592131/phosphorylated-4e-bp1-is-associated-with-tumor-progression-and-adverse-prognosis-in-colorectal-cancer
#6
Y Chen, J Wang, H Fan, J Xie, L Xu, B Zhou
Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E)- binding protein (4E-BP1) results in release of eIF4E, relieving translational repression and enhancing cancerigenic protein synthesis. This study aim to evaluate the level of phosphorylated 4E-BP1 (p-4E-BP1) in colorectal cancer (CRC) and to assess the cor-relation with clinicopathological factors and patient survival. The level of p-4E-BP1 was detected by immunohistochemistry and western bolt in patients with CRC. Then Cox regression model was used to evaluate the prognostic value of all covariates...
June 8, 2017: Neoplasma
https://www.readbyqxmd.com/read/28589219/-1-h-13-c-and-15-n-backbone-chemical-shift-assignments-of-4e-bp144-87-and-4e-bp144-87-bound-to-eif4e
#7
Naotaka Sekiyama, Andras Boeszoermenyi, Haribabu Arthanari, Gerhard Wagner, Mélissa Léger-Abraham
The eukaryotic translational initiation factor 4G (eIF4G) interacts with the cap-binding protein eIF4E through a consensus binding motif, Y(X)4LΦ (where X is any amino acid and Φ is a hydrophobic residue). 4E binding proteins (4E-BPs), which also contain a Y(X)4LΦ motif, regulate the eIF4E/eIF4G interaction. The non- or minimally-phosphorylated form of 4E-BP1 binds eIF4E, preventing eIF4E from interacting with eIF4G, thus inhibiting translation initiation. 4EGI-1, a small molecule inhibitor of the eIF4E/eIF4G interaction that is under investigation as a novel anti-cancer drug, has a dual activity; it disrupts the eIF4E/eIF4G interaction and stabilizes the binding of 4E-BP1 to eIF4E...
June 6, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28577281/acquired-tamoxifen-resistance-in-mcf-7-breast-cancer-cells-requires-hyperactivation-of-eif4f-mediated-translation
#8
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/28573908/the-eif4e-inhibitor-ribavirin-as-a-potential-antilymphoma-therapeutic-early-clinical-data
#9
Sarah C Rutherford, Eric N Stewart, Zhengming Chen, Amy Chadburn, Natasha E Wehrli, Koen van Besien, Peter Martin, Richard R Furman, John P Leonard, Leandro Cerchietti
No abstract text is available yet for this article.
June 2, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28570642/mycobacterium-tuberculosis-subverts-negative-regulatory-pathways-in-human-macrophages-to-drive-immunopathology
#10
Patience T Brace, Liku B Tezera, Magdalena K Bielecka, Toby Mellows, Diana Garay, Shuye Tian, Lucinda Rand, Justin Green, Sanjay Jogai, Andrew J Steele, Timothy M Millar, Tilman Sanchez-Elsner, Jon S Friedland, Christopher G Proud, Paul T Elkington
Tuberculosis remains a global pandemic and drives lung matrix destruction to transmit. Whilst pathways driving inflammatory responses in macrophages have been relatively well described, negative regulatory pathways are less well defined. We hypothesised that Mycobacterium tuberculosis (Mtb) specifically targets negative regulatory pathways to augment immunopathology. Inhibition of signalling through the PI3K/AKT/mTORC1 pathway increased matrix metalloproteinase-1 (MMP-1) gene expression and secretion, a collagenase central to TB pathogenesis, and multiple pro-inflammatory cytokines...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28559344/viral-and-cellular-mrna-specific-activators-harness-pabp-and-eif4g-to-promote-translation-initiation-downstream-of-cap-binding
#11
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/28554840/atorvastatin-augments-temozolomide-s-efficacy-in-glioblastoma-via-prenylation-dependent-inhibition-of-ras-signaling
#12
Peng Peng, Wei Wei, Cheng Long, Jingwen Li
Ras signaling is often dysregulated and plays essential roles for the maintenance of glioblastoma. The proper function of Ras depends largely on the appropriate post-translational modification termed prenylation. Targeting protein prenylation therefore represents an alternative therapeutic strategy in glioblastoma. In this study, we demonstrate that prenylation inhibition by atorvastatin is active against glioblastoma. Atorvastatin alone dose-dependently inhibits growth and survival of multiple glioblastoma cell lines...
May 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28550454/oncogenic-roles-of-the-pi3k-akt-mtor-axis
#13
Masahiro Aoki, Teruaki Fujishita
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP...
May 28, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28544394/muscle-metabolic-alterations-induced-by-genetic-ablation-of-4e-bp1-and-4e-bp2-in-response-to-diet-induced-obesity
#14
Olivier Le Bacquer, Kristell Combe, Christophe Montaurier, Jérôme Salles, Christophe Giraudet, Véronique Patrac, Carla Domingues-Faria, Christelle Guillet, Katie Louche, Yves Boirie, Nahum Sonenberg, Cédric Moro, Stéphane Walrand
SCOPE: In recent years, several studies reported the role of eIF4E-binding proteins (4E-BPs) on the development of diet-induced obesity and insulin resistance. Our aim was to investigate the effect of 4E-BP protein deletion on lipid accumulation and metabolism in skeletal muscle in response to a high fat diet-induced obesity in 4E-BP1/2 DKO mice. METHODS AND RESULTS: Diet-induced obesity engendered increased ectopic accumulation of lipotoxic species in skeletal muscle of 4E-BP1 and 4E-BP2 double-knockout mice (4E-BP1/2 DKO), namely diacylglycerols and ceramides...
May 21, 2017: Molecular Nutrition & Food Research
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
#15
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/28522457/structure-of-eif4e-in-complex-with-an-eif4g-peptide-supports-a-universal-bipartite-binding-mode-for-protein-translation
#16
Manuel Miras, Veronica Truniger, Cristina Silva, Nuria Verdaguer, Miguel A Aranda, Jordi Querol
The association-dissociation of the cap-binding protein eIF4E with eIF4G is a key control step in eukaryotic translation. The paradigm on the eIF4E-eIF4G interaction states that eIF4G binds to the dorsal surface of eIF4E through a single canonical alpha-helical motif, while metazoan 4E-BPs (m4E-BPs) advantageously compete against eIF4G thanks to a bi-modal binding onto the canonical but additionally to a non-canonical motif in the lateral eIF4E surface thus inhibiting translation. Very recently, it has been shown that metazoan eIF4Gs share this extended binding interface with m4E-BPs, with significant implications on the understanding of translation regulation and the design of therapeutic molecules...
May 18, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28521415/bioinformatics-analysis-of-dysregulated-micrornas-in-the-nipple-discharge-of-patients-with-breast-cancer
#17
Kai Zhang, Ya-Wen Wang, Rong Ma
MicroRNAs (miRNAs/miRs) have been reported to be associated with the tumorigenesis and progression of various types of human cancer; however, the underlying mechanisms of this association remain unclear. The aim of the present study was to explore the potential functions of miRNAs in the development of breast cancer using bioinformatics analysis, based on the miRNA expression profile in nipple discharge. A previous study demonstrated the upregulation of miR-3646 and miR-4484, and the downregulation of miR-4732-5p in the nipple discharge of patients with breast cancer, compared with patients with benign breast lesions...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28515298/crimean-congo-hemorrhagic-fever-virus-nucleocapsid-protein-augments-mrna-translation
#18
Subbiah Jeeva, Erdong Cheng, Safder S Ganaie, Mohammad A Mir
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne nairovirus of the Bunyaviridae family, causing severe illness with high mortality rates in humans. Here we demonstrate that CCHFV nucleocapsid protein (CCHFV-NP) augments mRNA translation. CCHFV-NP binds to the viral mRNA 5' UTR with high affinity. It facilitates the translation of reporter mRNA both in vivo and in vitro with the assistance of viral mRNA 5' UTR. CCHFV-NP equally favors the translation of both capped and uncapped mRNAs, demonstrating the independence of this translation strategy on the 5' cap...
May 17, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28504725/metformin-ameliorates-core-deficits-in-a-mouse-model-of-fragile-x-syndrome
#19
Ilse Gantois, Arkady Khoutorsky, Jelena Popic, Argel Aguilar-Valles, Erika Freemantle, Ruifeng Cao, Vijendra Sharma, Tine Pooters, Anmol Nagpal, Agnieszka Skalecka, Vinh T Truong, Shane Wiebe, Isabelle A Groves, Seyed Mehdi Jafarnejad, Clément Chapat, Elizabeth A McCullagh, Karine Gamache, Karim Nader, Jean-Claude Lacaille, Christos G Gkogkas, Nahum Sonenberg
Fragile X syndrome (FXS) is the leading monogenic cause of autism spectrum disorders (ASD). Trinucleotide repeat expansions in FMR1 abolish FMRP expression, leading to hyperactivation of ERK and mTOR signaling upstream of mRNA translation. Here we show that metformin, the most widely used drug for type 2 diabetes, rescues core phenotypes in Fmr1(-/y) mice and selectively normalizes ERK signaling, eIF4E phosphorylation and the expression of MMP-9. Thus, metformin is a potential FXS therapeutic.
June 2017: Nature Medicine
https://www.readbyqxmd.com/read/28499042/proteomic-analysis-reveals-changes-in-carbohydrate-and-protein-metabolism-associated-with-broiler-breast-myopathy
#20
Vivek A Kuttappan, Walter Bottje, Ranjith Ramnathan, Steven D Hartson, Craig N Coon, Byung-Whi Kong, Casey M Owens, Mercedes Vazquez-Añon, Billy M Hargis
White Striping (WS) and Woody Breast (WB) are 2 conditions that adversely affect consumer acceptance as well as quality of poultry meat and meat products. Both WS and WB are characterized with degenerative myopathic changes. Previous studies showed that WS and WB in broiler fillets could result in higher ultimate pH, increased drip loss, and decreased marinade uptake. The main objective of the present study was to compare the proteomic profiles of muscle tissue (n = 5 per group) with either NORM (no or few minor myopathic lesions) or SEV (with severe myopathic changes)...
May 12, 2017: Poultry Science
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