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https://www.readbyqxmd.com/read/29342219/the-expression-profile-and-prognostic-significance-of-eukaryotic-translation-elongation-factors-in-different-cancers
#1
Md Khurshidul Hassan, Dinesh Kumar, Monali Naik, Manjusha Dixit
Eukaryotic translation factors, especially initiation factors have garnered much attention with regards to their role in the onset and progression of different cancers. However, the expression levels and prognostic significance of translation elongation factors remain poorly explored in different cancers. In this study, we have investigated the mRNA transcript levels of seven translation elongation factors in different cancer types using Oncomine and TCGA databases. Furthermore, we have identified the prognostic significance of these factors using Kaplan-Meier Plotter and SurvExpress databases...
2018: PloS One
https://www.readbyqxmd.com/read/29337352/genetic-removal-of-eif2%C3%AE-kinase-perk-in-mice-enables-hippocampal-l-ltp-independent-of-mtorc1-activity
#2
Helena R Zimmermann, Wenzhong Yang, Brenna C Beckelman, Nicole P Kasica, Xueyan Zhou, Lucas Galli, Alexey G Ryazanov, Tao Ma
Characterization of the molecular signaling pathways underlying protein synthesis-dependent forms of synaptic plasticity, such as late long-term potentiation (L-LTP), can provide insights not only into memory expression/maintenance under physiological conditions but also potential mechanisms associated with the pathogenesis of memory disorders. Here, we report in mice that L-LTP failure induced by the mammalian (mechanistic) target of rapamycin complex 1 (mTORC1) inhibitor rapamycin is reversed by brain-specific genetic deletion of PKR-like ER kinase, PERK (PERK KO), a kinase for eukaryotic initiation factor 2α (eIF2α)...
January 16, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29300771/demonstration-of-translation-elongation-factor-3-activity-from-a-non-fungal-species-phytophthora-infestans
#3
Maria K Mateyak, Justyna K Pupek, Alexandra E Garino, McCllelan C Knapp, Sarah F Colmer, Terri Goss Kinzy, Stephen Dunaway
In most eukaryotic organisms, translation elongation requires two highly conserved elongation factors eEF1A and eEF2. Fungal systems are unique in requiring a third factor, the eukaryotic Elongation Factor 3 (eEF3). For decades, eEF3, a ribosome-dependent ATPase, was considered "fungal-specific", however, recent bioinformatics analysis indicates it may be more widely distributed among other unicellular eukaryotes. In order to determine whether divergent eEF3-like proteins from other eukaryotic organisms can provide the essential functions of eEF3 in budding yeast, the eEF3-like proteins from Schizosaccharomyes pombe and an oomycete, Phytophthora infestans, were cloned and expressed in Saccharomyces cerevisiae...
2018: PloS One
https://www.readbyqxmd.com/read/29288744/metabolic-suppression-in-the-pelagic-crab-pleuroncodes-planipes-in-oxygen-minimum-zones
#4
Brad A Seibel, Bryan E Luu, Shannon N Tessier, Trisha Towanda, Kenneth B Storey
The pelagic red crab, Pleuroncodes planipes, is abundant throughout the Eastern Tropical Pacific in both benthic and pelagic environments to depths of several hundred meters. The oxygen minimum zones in this region reaches oxygen levels as low as 0.1kPa at depths within the crabs vertical range. Crabs maintain aerobic metabolism to a critical PO2 of ~0.27±0.2kPa (10°C), in part by increasing ventilation as oxygen declines. At subcritical oxygen levels, they enhance anaerobic ATP production slightly as indicated by modest increases in lactate levels...
December 27, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29283292/morphological-molecular-and-hormonal-adaptations-to-early-morning-versus-afternoon-resistance-training
#5
Milan Sedliak, Michal Zeman, Gabriel Buzgó, Jan Cvecka, Dusan Hamar, Eugen Laczo, Monika Okuliarova, Marian Vanderka, Tomas Kampmiller, Keijo Häkkinen, Juha P Ahtiainen, Juha J Hulmi, Tormod S Nilsen, Håvard Wiig, Truls Raastad
It has been clearly established that maximal force and power is lower in the morning compared to noon or afternoon hours. This morning neuromuscular deficit can be diminished by regularly training in the morning hours. However, there is limited and contradictory information upon hypertrophic adaptations to time-of-day-specific resistance training. Moreover, no cellular or molecular mechanisms related to muscle hypertrophy adaptation have been studied with this respect. Therefore, the present study examined effects of the time-of-day-specific resistance training on muscle hypertrophy, phosphorylation of selected proteins, hormonal concentrations and neuromuscular performance...
December 28, 2017: Chronobiology International
https://www.readbyqxmd.com/read/29249217/palatal-tremor-revisited-disorder-with-nosological-diversity-and-etiological-heterogeneity
#6
Madhu Nagappa, Parayil S Bindu, Sanjib Sinha, Rose D Bharath, Mangalore Sandhya, Jitender Saini, Pavagada S Mathuranath, Arun B Taly
This case series aimed to describe clinicoradiological, electromyographic, and etiological spectra in palatal tremor (essential=1; symptomatic=26). Patients with symptomatic palatal tremor had 2 to 10 Hz arrhythmic electromyographic bursts, a spectrum of changes in inferior olivary nucleus, with/without lesions in Guillain Mollaret triangle, and varied etiologies (genetic=9, vascular=6, trauma=3, infections=3). Exome sequencing showed variations in POLG, WDR81, NDUFS8, TENM4, and EEF2. Clinical phenotypes of patients with POLG, WDR81, and NDUFS8 variations were consistent with that described in literature...
December 18, 2017: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
https://www.readbyqxmd.com/read/29235277/-targets-identification-and-mechanism-analysis-for-macrophage-activation-of-low-molecular-weight-saccharides-from-cistanche-deserticola-based-on-molecular-affinity-chromatography
#7
Li-Chao Wang, Dan Liu, Yong Jiang, Peng-Fei Tu, Ke-Wu Zeng
This study aims to investigate the targets and targets-involved mechanism for the macrophage activation of low molecular weight saccharides from Cistanche deserticola (LMSC). The phagocytic activity and NO release of RAW264.7 cells were detected, and results showed that LMSC exerts immune activation effect by significantly increasing the phagocytic activity and NO release. LMSC-conjugated epoxy-activated sepharose beads were prepared as affinity reagent to capture the target proteins. Twenty-four proteins such as Eef2 were identified by LC-MS/MS analysis...
October 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29235102/eukaryotic-elongation-factor-2-kinase-up-regulates-the-expression-of-proteins-implicated-in-cell-migration-and-cancer-cell-metastasis
#8
Jianling Xie, Kaikai Shen, Roman V Lenchine, Lee A Gethings, Paul J Trim, Marten F Snel, Ying Zhou, Justin W Kenney, Makoto Kamei, Marina Kochetkova, Xuemin Wang, Christopher G Proud
Eukaryotic elongation factor 2 kinase (eEF2K) negative regulates the elongation phase of mRNA translation and hence protein synthesis. Increasing evidence indicates that eEF2K plays an important role in the survival and migration of cancer cells and in tumour progression. As demonstrated by two-dimensional wound-healing and three-dimensional transwell invasion assays, knocking down or inhibiting eEF2K in cancer cells impairs migration and invasion of cancer cells. Conversely, exogenous expression of eEF2K or knocking down eEF2 (the substrate of eEF2K) accelerates wound healing and invasion...
December 13, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29172540/discovery-of-a-small-molecule-bromodomain-containing-protein-4-brd4-inhibitor-that-induces-amp-activated-protein-kinase-modulated-autophagy-associated-cell-death-in-breast-cancer
#9
Liang Ouyang, Lan Zhang, Jie Liu, Leilei Fu, Dahong Yao, Yuqian Zhao, Shouyue Zhang, Guan Wang, Gu He, Bo Liu
Upon the basis of The Cancer Genome Atlas (TCGA) data set, we identified that several autophagy-related proteins such as AMP-activated protein kinase (AMPK) were remarkably downregulated in breast cancer. Combined with coimmunoprecipitation assay, we demonstrated that BRD4 might interact with AMPK. After analyses of the pharmacophore and WPF interaction optimization, we designed a small-molecule inhibitor of BRD4, 9f (FL-411) which was validated by cocrystal structure with BD1 of BRD4. Subsequently, 9f was discovered to induce ATG5-dependent autophagy-associated cell death (ACD) by blocking BRD4-AMPK interaction and thus activating AMPK-mTOR-ULK1-modulated autophagic pathway in breast cancer cells...
December 7, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29069440/tight-interaction-of-eef2-in-the-presence-of-stm1-on-ribosome
#10
Hikari Hayashi, Riku Nagai, Taisho Abe, Miki Wada, Koichi Ito, Nono Takeuchi-Tomita
The stress-related protein Stm1 interacts with ribosomes, and is implicated in repressing translation. Stm1 was previously studied both in vivo and in vitro by cell-free translation systems using crude yeast lysates, but its precise functional mechanism remains obscure. Using an in vitro reconstituted translation system, we now show that Stm1 severely inhibits translation through its N-terminal region, aa 1 to 107, and this inhibition is antagonized by eEF3. We found that Stm1 stabilizes eEF2 on the 80S ribosome in the GTP-bound form, independently of eEF2's diphthamide modification, a conserved post-translational modification at the tip of domain IV...
October 23, 2017: Journal of Biochemistry
https://www.readbyqxmd.com/read/29051081/comparative-proteomic-analyses-using-itraq-labeling-provides-insights-into-fiber-diversity-in-sheep-and-goats
#11
Yan Li, Guangxian Zhou, Rui Zhang, Jiazhong Guo, Chao Li, Graeme Martin, Yulin Chen, Xiaolong Wang
The structural component of wool and hair fibers, such as keratin-associated proteins (KAPs), has been well described, but the genetic determinants of fiber diameter are largely unknown. Here, we have used an iTRAQ-based proteomic approach to investigate differences in protein abundance among 18 samples from sheep and goats across a diverse range of fibers. We identified proteins with different abundance and are associated with variation in fiber features. Proteins with different abundance are mainly keratin or keratin-associated proteins (KRTAP11-1, KRT6A, KRT38), or are related to hair growth (DSC2, DSG3, EEF2, CALML5, TCHH, SELENBP1) and fatty acid synthesis (FABP4, FABP5)...
October 16, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29024627/myostatin-inhibits-eef2k-eef2-by-regulating-ampk-to-suppress-protein-synthesis
#12
Zhao Deng, Pei Luo, Wen Lai, Tongxing Song, Jian Peng, Hong-Kui Wei
Growth of skeletal muscle is dependent on the protein synthesis, and the rate of protein synthesis is mainly regulated in the stage of translation initiation and elongation. Myostatin, a member of the transforming growth factor-β (TGF-β) superfamily, is a negative regulator of protein synthesis. C2C12 myotubes was incubated with 0, 0.01, 0.1, 1, 2, 3 μg/mL myostatin recombinant protein, and then we detected the rates of protein synthesis by the method of SUnSET. We found that high concentrations of myostatin (2 and 3 μg/mL) inhibited protein synthesis by blocking mTOR and eEF2K-eEF2 pathway, while low concentration of myostatin (0...
December 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28982725/human-skeletal-muscle-is-refractory-to-the-anabolic-effects-of-leucine-during-the-postprandial-muscle-full-period-in-older-men
#13
W Kyle Mitchell, Bethan E Phillips, Ian Hill, Paul Greenhaff, Jonathan N Lund, John P Williams, Debbie Rankin, Daniel J Wilkinson, Kenneth Smith, Philip J Atherton
Leucine modulates muscle protein synthesis (MPS), with potential to facilitate accrual/maintenance of muscle mass. Animal models suggest that leucine boluses shortly after meals may prolong MPS and delay onset of a "muscle-full" state. However, the effects of nutrient "top-ups" in humans, and particularly older adults where deficits exist, have not been explored. We determined the effects of a leucine top-up after essential amino acid (EAA) feeding on anabolic signaling, MPS, and muscle energy metabolism in older men...
November 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28938523/hypothermia-induced-by-anesthesia-regulates-various-signals-expressions-in-the-hippocampus-of-animals
#14
Huimei Hao, Shanshan Wang
Though important for a variety of medical procedures, general anesthesia is not a problem free. Some anesthetics have been suggested to affect a number of signals, which are associated with memory consolidation and cognition. In the present study, we attempted to investigate the molecular mechanism of anesthesia-regulated processes. We found that under hypothermic condition, anesthetic of isoflurane enhances various signals expression in hippocampus, including Hspd1, Actb, Mgst1, THBS4, Syp, C1QC, Serpine, Plat, and Ngf, which were related to cellular stress, neural plasticity responses, and hippocampal injury...
November 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28913610/eukaryotic-elongation-factor-2-eef2-is-a-potential-biomarker-of-prostate-cancer
#15
Xuefeng Zhang, Linkun Hu, Mingzhan Du, Xuedong Wei, Jun Zhang, Yu Hui, Cheng Chen, Gang Li, Jianquan Hou
Eukaryotic elongation factor 2 (eEF2), a key regulator of protein synthesis, is involved in the progression of several types of cancer. This first study was to investigate the relationships between eEF2 protein and prostate cancer (PCa). Immunohistochemical staining was used to verify eEF2 protein in a set of 97 formalin-fixed, paraffin-embedded primary PCa tissues. Expression of eEF2 protein in positive cells was characterized by cytoplasmic staining. Correlations with clinicopathological factors were evaluated by Chi-square or Fisher's exact probability tests...
September 14, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28846937/a-novel-imp1-inhibitor-btynb-targets-c-myc-and-inhibits-melanoma-and-ovarian-cancer-cell-proliferation
#16
Lily Mahapatra, Neal Andruska, Chengjian Mao, Jeremy Le, David J Shapiro
The oncofetal mRNA-binding protein, IMP1 or insulin-like growth factor-2 mRNA-binding protein 2 (IGF2BP1), binds to and stabilizes c-Myc, β-TrCP1, and other oncogenic mRNAs, leading to increased expression of the proteins encoded by its target mRNAs. IMP1 is frequently overexpressed in cancer and is strongly correlated with a poor prognosis and reduced survival in melanoma, ovarian, breast, colon, and lung cancer. While IMP1 is an attractive anticancer drug target, there are no small molecule inhibitors of IMP1...
October 2017: Translational Oncology
https://www.readbyqxmd.com/read/28833775/glucagon-like-peptide-1-cleavage-product-glp-1-9-36-amide-enhances-hippocampal-long-term-synaptic-plasticity-in-correlation-with-suppression-of-kv4-2-expression-and-eef2-phosphorylation
#17
Stephen M Day, Wenzhong Yang, Sarah Ewin, Xueyan Zhou, Tao Ma
Glucagon-like peptide-1 (GLP-1) is an endogenous gut hormone and a key regulator in maintaining glucose homeostasis by stimulating insulin secretion. Its natural cleavage product GLP-1 (9-36), used to be considered a "bio-inactive" metabolite mainly because of its lack of insulinotropic effects and low affinity for GLP-1 receptors, possesses unique properties such as anti-oxidant and cardiovascular protection. Little is known about the role of GLP-1 (9-36) in central nervous system. Here we report that chronic, systemic application of GLP-1 (9-36) in adult mice facilitated both the induction and maintenance phases of hippocampal long-term potentiation (LTP), a major form of synaptic plasticity...
August 18, 2017: Hippocampus
https://www.readbyqxmd.com/read/28804461/the-effect-of-resistance-exercise-on-inflammatory-and-myogenic-markers-in-patients-with-chronic-kidney-disease
#18
Emma L Watson, Joao L Viana, David Wimbury, Naomi Martin, Neil J Greening, Jonathan Barratt, Alice C Smith
Background: Muscle wasting is a common complication of Chronic Kidney Disease (CKD) and is clinically important given its strong association with morbidity and mortality in many other chronic conditions. Exercise provides physiological benefits for CKD patients, however the molecular response to exercise remains to be fully determined. We investigated the inflammatory and molecular response to resistance exercise before and after training in these patients. Methods: This is a secondary analysis of a randomized trial that investigated the effect of 8 week progressive resistance training on muscle mass and strength compared to non-exercising controls...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28775286/elp3-and-dph3-of-schizosaccharomyces-pombe-mediate-cellular-stress-responses-through-trna-lys-uuu-modifications
#19
Desirée Villahermosa, Oliver Fleck
Efficient protein synthesis in eukaryotes requires diphthamide modification of translation elongation factor eEF2 and wobble uridine modifications of tRNAs. In higher eukaryotes, these processes are important for preventing neurological and developmental defects and cancer. In this study, we used Schizosaccharomyces pombe as a model to analyse mutants defective in eEF2 modification (dph1Δ), in tRNA modifications (elp3Δ), or both (dph3Δ) for sensitivity to cytotoxic agents and thermal stress. The dph3Δ and elp3Δ mutants were sensitive to a range of drugs and had growth defects at low temperature...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28726101/eukaryotic-elongation-factor-2-kinase-activation-in-m-soleus-under-14-day-hindlimb-unloading-of-rats
#20
Y N Lomonosova, S P Belova, T M Mirzoev, I B Kozlovskaya, B S Shenkman
Functional unloading of m. soleus of male Wistar rats was found to cause a reduction in protein synthesis. The level of phosphorylation of the translation elongation factor 2 (eEF2) and the eEF2 kinase (eEF2k) activity in m. soleus after 14 days of unloading were assessed. Rats were divided into the control group (C) and the group with hindlimb unloading for 14 days (HU14). The level of eEF2 phosphorylation in group HU14 was 80%, whereas in the control is was 40%. The indices of eEF2k expression and protein content in group HU14 increased compared to group C...
May 2017: Doklady. Biochemistry and Biophysics
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