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https://www.readbyqxmd.com/read/28522457/structure-of-eif4e-in-transcriptional-complex-with-an-eif4g-peptide-supports-a-universal-bipartite-binding-mode-for-protein-translation
#1
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
#2
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
#3
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
#4
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.
May 15, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28499042/proteomic-analysis-reveals-changes-in-carbohydrate-and-protein-metabolism-associated-with-broiler-breast-myopathy
#5
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
https://www.readbyqxmd.com/read/28493823/hepatitis-c-virus-core-protein-targets-4e-bp1-expression-and-phosphorylation-and-potentiates-myc-induced-liver-carcinogenesis-in-transgenic-mice
#6
Cosette Abdallah, Charlène Lejamtel, Nassima Benzoubir, Serena Battaglia, Nazha Sidahmed-Adrar, Christophe Desterke, Matthieu Lemasson, Arielle R Rosenberg, Didier Samuel, Christian Bréchot, Delphine Pflieger, François Le Naour, Marie-Françoise Bourgeade
Hepatitis C virus (HCV) is a leading cause of liver diseases including the development of hepatocellular carcinoma (HCC). Particularly, core protein has been involved in HCV-related liver pathologies. However, the impact of HCV core on signaling pathways supporting the genesis of HCC remains largely elusive. To decipher the host cell signaling pathways involved in the oncogenic potential of HCV core, a global quantitative phosphoproteomic approach was carried out. This study shed light on novel differentially phosphorylated proteins, in particular several components involved in translation...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28491073/regulation-of-translation-by-tor-eif4e-and-eif2%C3%AE-in-plants-current-knowledge-challenges-and-future-perspectives
#7
REVIEW
Ane Sesma, Carmen Castresana, M Mar Castellano
An important step in eukaryotic gene expression is the synthesis of proteins from mRNA, a process classically divided into three stages, initiation, elongation, and termination. Translation is a precisely regulated and conserved process in eukaryotes. The presence of plant-specific translation initiation factors and the lack of well-known translational regulatory pathways in this kingdom nonetheless indicate how a globally conserved process can diversify among organisms. The control of protein translation is a central aspect of plant development and adaptation to environmental stress, but the mechanisms are still poorly understood...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28487484/cap-binding-protein-4ehp-effects-translation-silencing-by-micrornas
#8
Clément Chapat, Seyed Mehdi Jafarnejad, Edna Matta-Camacho, Geoffrey G Hesketh, Idit A Gelbart, Jan Attig, Christos G Gkogkas, Tommy Alain, Noam Stern-Ginossar, Marc R Fabian, Anne-Claude Gingras, Thomas F Duchaine, Nahum Sonenberg
MicroRNAs (miRNAs) play critical roles in a broad variety of biological processes by inhibiting translation initiation and by destabilizing target mRNAs. The CCR4-NOT complex effects miRNA-mediated silencing, at least in part through interactions with 4E-T (eIF4E transporter) protein, but the precise mechanism is unknown. Here we show that the cap-binding eIF4E-homologous protein 4EHP is an integral component of the miRNA-mediated silencing machinery. We demonstrate that the cap-binding activity of 4EHP contributes to the translational silencing by miRNAs through the CCR4-NOT complex...
May 9, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28487214/eif4e-phosphorylation-by-mst1-reduces-translation-of-a-subset-of-mrnas-but-increases-lncrna-translation
#9
Kyung-Won Min, Sylvia Davila, Richard W Zealy, Lawson T Lloyd, In Young Lee, Rumi Lee, Kyung Hye Roh, Ahjin Jung, Jacek Jemielity, Eui-Ju Choi, Jeong Ho Chang, Je-Hyun Yoon
Post-transcriptional gene regulation is an important step in eukaryotic gene expression. The last step to govern production of nascent peptides is during the process of mRNA translation. mRNA translation is controlled by many translation initiation factors that are susceptible to post-translational modifications. Here we report that one of the translation initiation factors, eIF4E, is phosphorylated by Mammalian Ste20-like kinase (MST1). Upon phosphorylation, eIF4E weakly interacts with the 5' CAP to inhibit mRNA translation...
May 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28484016/social-propinquity-in-rodents-as-measured-by-tube-cooccupancy-differs-between-inbred-and-outbred-genotypes
#10
Alexander H Tuttle, Shannon Tansley, Kimberly Dossett, Sarasa Tohyama, Arkady Khoutorsky, Sioui Maldonado-Bouchard, Liane Stein, Lindsey Gerstein, Hayley Crawhall-Duk, Rebecca Pearl, Melissa Sukosd, Philip Leger, Oliver M Hardt, David Yachnin, Jean-Sebastien Austin, Claire M Chan, Tine Pooters, Isabelle Groves, Loren J Martin, Nahum Sonenberg, Christos G Gkogkas, Jeffrey S Mogil
Existing assays of social interaction are suboptimal, and none measures propinquity, the tendency of rodents to maintain close physical proximity. These assays are ubiquitously performed using inbred mouse strains and mutations placed on inbred genetic backgrounds. We developed the automatable tube cooccupancy test (TCOT) based on propinquity, the tendency of freely mobile rodents to maintain close physical proximity, and assessed TCOT behavior on a variety of genotypes and social and environmental conditions...
May 8, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28468879/regulation-of-tacaribe-mammarenavirus-translation-positive-5-and-negative-3-elements-and-role-of-key-cellular-factors
#11
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/28461486/brd4-modulates-the-innate-immune-response-through-mnk2-eif4e-pathway-dependent-translational-control-of-i%C3%AE%C2%BAb%C3%AE
#12
Yan Bao, Xuewei Wu, Jinjing Chen, Xiangming Hu, Fuxing Zeng, Jianjun Cheng, Hong Jin, Xin Lin, Lin-Feng Chen
Bromodomain-containing factor Brd4 has emerged as an important transcriptional regulator of NF-κB-dependent inflammatory gene expression. However, the in vivo physiological function of Brd4 in the inflammatory response remains poorly defined. We now demonstrate that mice deficient for Brd4 in myeloid-lineage cells are resistant to LPS-induced sepsis but are more susceptible to bacterial infection. Gene-expression microarray analysis of bone marrow-derived macrophages (BMDMs) reveals that deletion of Brd4 decreases the expression of a significant amount of LPS-induced inflammatory genes while reversing the expression of a small subset of LPS-suppressed genes, including MAP kinase-interacting serine/threonine-protein kinase 2 (Mknk2)...
May 16, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28461326/eif2%C3%AE-phosphorylation-mediates-il24-induced-apoptosis-through-inhibition-of-translation
#13
Leah Persaud, Xuelin Zhong, Giselle Alvarado, Winchie Do, Jordan Dejoie, Anna Zybtseva, Bertal H Aktas, Moira Sauane
Interleukin 24 (IL-24) is an immunomodulatory cytokine that also displays broad cancer-specific suppressor effects. The tumor suppressor activities of IL-24 include inhibition of angiogenesis, sensitization to chemotherapy, and cancer-specific apoptosis. Supra-physiologic activation and/or overexpression of translation initiation factors are implicated in the initiation and progression of cancer animal models as well as a subset of human cancers. Activation and/or overexpression of translation initiation factors correlate with aggressiveness of cancer and poor prognosis...
May 1, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28447756/matrine-reduces-the-proliferation-of-a549%C3%A2-cells-via-the-p53-p21-pcna-eif4e-signaling-pathway
#14
Zhiyan Lu, Youzhang Xiao, Xing Liu, Zaipeng Zhang, Feng Xiao, Yongyi Bi
The aim of the present study was to investigate how matrine affects the proliferation of A549 human lung adenocarcinoma cells via the p53/p21/proliferating cell nuclear antigen (PCNA)/eukaryotic translation initiation factor 4E (eIF4E) signaling pathway. The effect of different concentrations of matrine on the proliferation of A549 cells was investigated using a 3‑(4,5‑dimethylthiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide (MTT) assay. The migration of A549 cells following exposure to varied concentrations of matrine was detected using a Transwell cell migration assay...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28428059/the-decreased-growth-performance-and-impaired-immune-function-and-structural-integrity-by-dietary-iron-deficiency-or-excess-are-associated-with-tor-nf-%C3%AE%C2%BAb-p38mapk-nrf2-and-mlck-signaling-in-head-kidney-spleen-and-skin-of-grass-carp-ctenopharyngodon-idella
#15
Yan-Lin Guo, Wei-Dan Jiang, Pei Wu, Yang Liu, Xiao-Qiu Zhou, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Lin Feng
This study was conducted to investigate the effects of dietary iron on the growth, and immune function and structural integrity in head kidney, spleen and skin as well as the underlying signaling of young grass carp (Ctenopharyngodon idella). Total 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 mg/kg (diets 2-6 were added with ferrous fumarate) and 73.50 mg/kg (diet 7 was added with ferrous sulfate) diet for 60 days...
April 18, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28423550/quantitative-proteomic-analysis-of-gastric-cancer-tissue-reveals-novel-proteins-in-platelet-derived-growth-factor-b-signaling-pathway
#16
Fang Liu, Yuan Zhang, Tingting Men, Xingyue Jiang, Chunhua Yang, He Li, Xiaodan Wei, Dong Yan, Gangming Feng, Jianke Yang, Jonas Bergquist, Bin Wang, Wenguo Jiang, Jia Mi, Geng Tian
Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28417568/cisplatin-resistant-cancer-cells-are-sensitive-to-aurora-kinase-a-inhibition-by-alisertib
#17
Lihong Wang, Janet Arras, Ahmed Katsha, Saif Hamdan, Abbes Belkhiri, Jeffrey Ecsedy, Wael El-Rifai
De novo and acquired resistance to platinum therapy such as cisplatin (CDDP) is a clinical challenge in gastric cancer treatment. Aberrant expression and activation of Aurora kinase A (AURKA) and eukaryotic translation initiation factor 4E (eIF4E) are detected in several cancer types. Herein, we investigated the role of AURKA in CDDP resistance in gastric cancer. Western blot analysis demonstrated overexpression of AURKA and phosphorylation of eIF4E in acquired and de novo CDDP-resistant gastric cancer models...
April 18, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28415825/recombinant-human-erythropoietin-stimulates-melanoma-tumor-growth-through-activation-of-initiation-factor-eif4e
#18
Annabelle Julius, Anjali Desai, Raymond L Yung
Recombinant human erythropoietin (EPO) is standard treatment for anemia in cancer patients. Recent clinical trials suggest that EPO may accelerate tumor progression and increase mortality. However, the evidence supporting a growth-promoting effect of EPO has remained controversial. Employing an in vivo model of B16 murine melanoma, we observed that administration of EPO to tumor bearing C57BL/6 mice resulted in pronounced acceleration of melanoma growth. Our in vitro studies demonstrate that B16 murine melanoma cells express EPOR, both at the protein and mRNA levels...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408475/regulation-of-human-immunodeficiency-virus-type-1-hiv-1-mrna-translation
#19
REVIEW
Laura Hidalgo, Chad M Swanson
Human immunodeficiency virus type 1 (HIV-1) mRNA translation is a complex process that uses the host translation machinery to synthesise viral proteins. Several mechanisms for HIV-1 mRNA translation initiation have been proposed including (1) cap-dependent, eIF4E-dependent, (2) cap-dependent, cap-binding complex-dependent, (3) internal ribosome entry sites, and (4) ribosome shunting. While these mechanisms promote HIV-1 mRNA translation in the context of in vitro systems and subgenomic constructs, there are substantial knowledge gaps in understanding how they regulate viral protein production in the context of full-length virus infection...
April 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28395726/-over-expressions-of-p-eif4e-and-p-4ebp1-are-associated-with-poor-prognosis-in-nasopharyngeal-carcinoma
#20
Jun Zheng, Chunyan Zhang, Yiqiang Zhang, Jinhong Pei, Songqing Fan
Objective To observe the expressions of phosphorylated eukaryotic translation initiation factor 4E (p-eIF4E) and phospho-eIF4E-binding protein 1 (p-4EBP1) and investigate their associations with clinicopathological features and prognosis in nasopharyngeal carcinoma (NPC). Methods We detected the expressions of p-eIF4E and p-4EBP1 proteins by immunohistochemistry in NPC tissues (n=314 cases), and analyzed the associations between the expressions of p-eIF4E and p-4EBP1 proteins and clinicopathological features and prognosis in NPC by SPSS16...
April 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
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