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https://www.readbyqxmd.com/read/28918902/mtor-controls-mitochondrial-dynamics-and-cell-survival-via-mtfp1
#1
Masahiro Morita, Julien Prudent, Kaustuv Basu, Vanessa Goyon, Sakie Katsumura, Laura Hulea, Dana Pearl, Nadeem Siddiqui, Stefan Strack, Shawn McGuirk, Julie St-Pierre, Ola Larsson, Ivan Topisirovic, Hojatollah Vali, Heidi M McBride, John J Bergeron, Nahum Sonenberg
The mechanisms that link environmental and intracellular stimuli to mitochondrial functions, including fission/fusion, ATP production, metabolite biogenesis, and apoptosis, are not well understood. Here, we demonstrate that the nutrient-sensing mechanistic/mammalian target of rapamycin complex 1 (mTORC1) stimulates translation of mitochondrial fission process 1 (MTFP1) to control mitochondrial fission and apoptosis. Expression of MTFP1 is coupled to pro-fission phosphorylation and mitochondrial recruitment of the fission GTPase dynamin-related protein 1 (DRP1)...
September 13, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28916625/transcriptional-correlates-of-memory-maintenance-following-long-term-sensitization-of-aplysia-californica
#2
Catherine Conte, Samantha Herdegen, Saman Kamal, Jency Patel, Ushma Patel, Leticia Perez, Marissa Rivota, Robert J Calin-Jageman, Irina E Calin-Jageman
We characterized the transcriptional response accompanying maintenance of long-term sensitization (LTS) memory in the pleural ganglia of Aplysia californica using microarray (N = 8) and qPCR (N = 11 additional samples). We found that 24 h after memory induction there is strong regulation of 1198 transcripts (748 up and 450 down) in a pattern that is almost completely distinct from what is observed during memory encoding (1 h after training). There is widespread up-regulation of transcripts related to all levels of protein production, from transcription (e...
October 2017: Learning & Memory
https://www.readbyqxmd.com/read/28915586/hepatitis-c-virus-core-protein-targets-4e-bp1-expression-and-phosphorylation-and-potentiates-myc-induced-liver-carcinogenesis-in-transgenic-mice
#3
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...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913664/supplementation-of-enzyme-treated-soy-protein-saves-dietary-protein-and-promotes-digestive-and-absorptive-ability-referring-to-tor-signaling-in-juvenile-fish
#4
Weiwei Xiao, Weidan Jiang, Lin Feng, Yang Liu, Pei Wu, Jun Jiang, Yongan Zhang, Xiaoqiu Zhou
This study was conducted to evaluate the effect of enzyme-treated soy protein (ETSP) supplementation in the low-protein diet on growth performance, digestive and absorptive capacities, and related signaling molecules' gene expressions in juvenile Jian carp. The results showed that percent weight gain (PWG), specific growth rate (SGR), and feed intake (FI) were decreased by reducing dietary protein from 34 to 32% (P < 0.05). Supplying low-protein diet with optimal ETSP increased previously mentioned indices of juvenile Jian carp (P < 0...
September 14, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28887716/inhibitory-effect-and-molecular-mechanism-of-mesenchymal-stem-cells-on-nsclc-cells
#5
Mengwu Pan, Lingling Hou, Jingsi Zhang, Diandian Zhao, Jilei Hua, Ziling Wang, Jinsheng He, Hong Jiang, Honggang Hu, Lishu Zhang
Non-small-cell lung cancer (NSCLC) is still the main threat of cancer-associated death. Current treatment of NSCLC has limited effectiveness, and unfortunately, the prognosis of NSCLC remains poor. Therefore, a novel strategy for cancer therapy is urgently needed. Stem cell therapy has significant potential for cancer treatment. Mesenchymal stem cells (MSCs) with capacity for self-renewal and differentiation into various cells types exhibit the feature of homing to tumor site and immunosuppression, have been explored as a new treatment for various cancers...
September 8, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28881737/galeterone-and-its-analogs-inhibit-mnk-eif4e-axis-synergize-with-gemcitabine-impede-pancreatic-cancer-cell-migration-invasion-and-proliferation-and-inhibit-tumor-growth-in-mice
#6
Andrew K Kwegyir-Afful, Francis N Murigi, Puranik Purushottamachar, Vidya P Ramamurthy, Marlena S Martin, Vincent C O Njar
Survival rate for pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) is poor, with about 80% of patients presenting with the metastatic disease. Gemcitabine, the standard chemotherapeutic agent for locally advanced and metastatic PDAC has limited efficacy, attributed to innate/acquired resistance and activation of pro-survival pathways. The Mnk1/2-eIF4E and NF-κB signaling pathways are implicated in PDAC disease progression/metastasis and also associated with gemcitabine-induced resistance in PDAC...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28881582/metformin-requires-4e-bps-to-induce-apoptosis-and-repress-translation-of-mcl-1-in-hepatocellular-carcinoma-cells
#7
Mamatha Bhat, Akiko Yanagiya, Tyson Graber, Nataliya Razumilava, Steve Bronk, Domenick Zammit, Yunhao Zhao, Chadi Zakaria, Peter Metrakos, Michael Pollak, Nahum Sonenberg, Gregory Gores, Maritza Jaramillo, Masahiro Morita, Tommy Alain
Metformin inhibits the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, which is frequently upregulated in hepatocellular carcinoma (HCC). Metformin has also been shown to induce apoptosis in this cancer. Here, we investigate whether metformin-induced apoptosis in HCC is mediated by the downstream mTORC1 effectors eukaryotic initiation factor 4E and (eIF4E)-binding proteins (4E-BPs). Further, we ask whether changes in 4E-BPs activity during metformin treatment negatively regulate translation of the anti-apoptotic myeloid cell leukemia 1 (Mcl-1) mRNA...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878291/map-kinase-interacting-serine-threonine-kinase-2-promotes-proliferation-metastasis-and-predicts-poor-prognosis-in-non-small-cell-lung-cancer
#8
Zhihua Guo, Guilin Peng, Ermao Li, Shaoyan Xi, Yu Zhang, Yong Li, Xiaodong Lin, Guangqiu Li, Qinian Wu, Jianxing He
We hypothesized that MAP kinase-interacting serine/threonine kinase 2 (MNK2) may contribute to non-small cell lung cancer (NSCLC) development, and serve as a new therapeutic target. Immunohistochemical staining evaluated the correlation between MNK2 expression and clinicopathological features in 367 NSCLC cancer tissues. We determined the effects of MNK2 silencing in NSCLC cell lines in vitro and in vivo. RT-PCR and western blotting was used to examine the impact of MNK2 on ERK and AKT pathways. MNK2 was overexpressed in NSCLC cell lines and tumor tissues...
September 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28864377/antiviral-drug-ribavirin-targets-thyroid-cancer-cells-by-inhibiting-the-eif4e-%C3%AE-catenin-axis
#9
Xiawei Shen, Yali Zhu, Zuixuan Xiao, Xuemei Dai, Dan Liu, Lin Li, Baolai Xiao
BACKGROUND: Although eukaryotic translation initiation factor 4E (eIF4E) is important in cancer development and progression, its role in thyroid cancer is not well understood. Ribavirin, an anti-viral drug, has been identified as an eIF4E inhibitor. Herein, we investigated the effects of ribavirin on thyroid cancer and its molecular mechanisms of action. MATERIALS AND METHODS: The effects of ribavirin on thyroid cancer was investigated using in vitro cellular assays and in vivo xenograft mouse model...
August 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28858511/anchimerically-activated-protides-as-inhibitors-of-cap-dependent-translation-and-inducers-of-chemosensitization-in-mantle-cell-lymphoma
#10
Aniekan Okon, JingJing Han, Surendra Dawadi, Christos Demosthenous, Courtney C Aldrich, Mamta Gupta, Carston R Wagner
The cellular delivery of nucleotides through various pronucleotide strategies has expanded the utility of nucleosides as a therapeutic class. Although highly successful, the highly popular ProTide system relies on a four-step enzymatic and chemical process to liberate the corresponding monophosphate. To broaden the scope and reduce the number of steps required for monophosphate release, we have developed a strategy that depends on initial chemical activation by a sulfur atom of a methylthioalkyl protecting group, followed by enzymatic hydrolysis of the resulting phosphoramidate monoester...
September 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28854595/dormancy-and-activation-of-human-oocytes-from-primordial-and-primary-follicles-molecular-clues-to-oocyte-regulation
#11
E H Ernst, M L Grøndahl, S Grund, K Hardy, A Heuck, L Sunde, S Franks, C Y Andersen, P Villesen, K Lykke-Hartmann
STUDY QUESTION: Do specific transcriptome dynamics in human oocytes from primordial and primary follicles identify novel pathways in oocyte activation? SUMMARY ANSWER: The transcriptomic profiles in oocytes from primordial and primary follicles, respectively, revealed several new canonical pathways as putative mediators of oocyte dormancy and activation. WHAT IS KNOWN ALREADY: Cellular signaling pathways including PI3K/AKT and AKT/mTOR as well as TGF-β and IGF signaling are known to regulate the primordial-to-primary transition in mammalian follicle development...
August 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28852129/a-novel-function-of-ciap1-as-a-mediator-of-chip-driven-eif4e-regulation
#12
Tae Woong Seo, Ji Sun Lee, Ye Na Choi, Dar Heum Jeong, Sun Kyung Lee, Soon Ji Yoo
eIF4E is an initiator protein in cap-dependent translation. Its overexpression is linked to tumorigenesis in various human cancers, suggesting that the levels of eIF4E must be under tight control in normal cells. Although several eIF4E regulatory mechanisms have been demonstrated, the intracellular mechanisms controlling eIF4E protein levels remain poorly understood. Here, we report that eIF4E is efficiently regulated by dual mechanisms, both involving human inhibitor of apoptosis family protein cIAP1. cIAP1 itself ubiquitinates eIF4E as an E3 ligase, and interestingly, cIAP1 also functions as a mediator to present eIF4E to another E3 ligase, CHIP...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28843814/interaction-of-2a-proteinase-of-human-rhinovirus-genetic-group-a-with-eif4e-is-required-for-eif4g-cleavage-during-infection
#13
Martina Aumayr, Anna Schrempf, Öykü Üzülmez, Karin M Olek, Tim Skern
In enteroviruses, the inhibition of protein synthesis from capped host cell mRNA is catalyzed by the virally encoded 2A proteinase (2A(pro)), which cleaves eukaryotic initiation factors (eIF) 4GI and 4GII. Despite much investigation, the exact mechanism of 2A(pro) cleavage remains however unclear. Here, we identify the domains responsible for the eIF4E/HRV2 2A(pro) interaction using molecular modelling and describe mutations that impair this interaction and delay in vitro cleavage of eIF4G isoforms. Furthermore, we produced HRV1A viruses bearing the mutation L17R, Y32A or Y86A in the 2A(pro) sequence...
August 24, 2017: Virology
https://www.readbyqxmd.com/read/28841037/dual-abrogation-of-mnk-and-mtor-a-novel-therapeutic-approach-for-the-treatment-of-aggressive-cancers
#14
Ella Lineham, John Spencer, Simon J Morley
Targeting the translational machinery has emerged as a promising therapeutic option for cancer treatment. Cancer cells require elevated protein synthesis and exhibit augmented activity to meet the increased metabolic demand. Eukaryotic translation initiation factor 4E is necessary for mRNA translation, its availability and phosphorylation are regulated by the PI3K/AKT/mTOR and MNK1/2 pathways. The phosphorylated form of eIF4E drives the expression of oncogenic proteins including those involved in metastasis...
August 25, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28827335/cellular-cap-binding-protein-eif4e-promotes-picornavirus-genome-restructuring-and-translation
#15
Brian C Avanzino, Gabriele Fuchs, Christopher S Fraser
Picornaviruses use internal ribosome entry sites (IRESs) to translate their genomes into protein. A typical feature of these IRESs is their ability to bind directly to the eukaryotic initiation factor (eIF) 4G component of the eIF4F cap-binding complex. Remarkably, the hepatitis A virus (HAV) IRES requires eIF4E for its translation, but no mechanism has been proposed to explain this. Here we demonstrate that eIF4E regulates HAV IRES-mediated translation by two distinct mechanisms. First, eIF4E binding to eIF4G generates a high-affinity binding conformation of the eIF4F complex for the IRES...
August 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28811467/the-mtorc1-4e-bp-eif4e-axis-controls-de-novo-bcl6-protein-synthesis-in-t-cells-and-systemic-autoimmunity
#16
Woelsung Yi, Sanjay Gupta, Edd Ricker, Michela Manni, Rolf Jessberger, Yurii Chinenov, Henrik Molina, Alessandra B Pernis
Post-transcriptional modifications can control protein abundance, but the extent to which these alterations contribute to the expression of T helper (TH) lineage-defining factors is unknown. Tight regulation of Bcl6 expression, an essential transcription factor for T follicular helper (TFH) cells, is critical as aberrant TFH cell expansion is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE). Here we show that lack of the SLE risk variant Def6 results in deregulation of Bcl6 protein synthesis in T cells as a result of enhanced activation of the mTORC1-4E-BP-eIF4E axis, secondary to aberrant assembly of a raptor-p62-TRAF6 complex...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28803610/two-distinct-nodes-of-translational-inhibition-in-the-integrated-stress-response
#17
Hyung Don Ryoo, Deepika Vasudevan
The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated eIF2α kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor eIF2α...
August 14, 2017: BMB Reports
https://www.readbyqxmd.com/read/28797816/kinetic-analyses-of-phosphorylated-and-non-phosphorylated-eifiso4e-binding-to-mrna-cap-analogues
#18
Mateen A Khan, Dixie J Goss
Phosphorylation of eukaryotic initiation factors was previously shown to interact with m(7)G cap and play an important role in the regulation of translation initiation of protein synthesis. To gain further insight into the phosphorylation process of plant protein synthesis, the kinetics of phosphorylated wheat eIFiso4E binding to m(7)G cap analogues were examined. Phosphorylation of wheat eIFiso4E showed similar kinetic effects to human eIF4E binding to m(7)-G cap. Phosphorylation of eIFiso4E decreased the kinetic rate (2-fold) and increased the dissociation rate (2-fold) as compared to non-phosphorylated eIFiso4E binding to both mono- and di-nucleotide analogues at 22°C...
August 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28790888/amyloid-%C3%AE-1-42-a%C3%AE-1-42-induces-the-cdk2-mediated-phosphorylation-of-tau-through-the-activation-of-the-mtorc1-signaling-pathway-while-promoting-neuronal-cell-death
#19
Ki Hoon Lee, Sei-Jung Lee, Hyun Jik Lee, Gee Euhn Choi, Young Hyun Jung, Dah Ihm Kim, Amr Ahmed Gabr, Jung Min Ryu, Ho Jae Han
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by cognitive impairment and memory loss. Amyloid β1-42 (Aβ) and hyper-phosphorylation of microtubule-associated protein tau have been considered as major histological features in AD. However, the mechanism of how Aβ induces the hyper-phosphorylation of tau remains to be clarified. In the present study, we investigated the underlying cellular mechanisms of Aβ with regard to the cell cycle regulatory protein-mediated phosphorylation of tau in promoting neuronal cell death...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28771520/variations-of-five-eif4e-genes-across-cassava-accessions-exhibiting-tolerant-and-susceptible-responses-to-cassava-brown-streak-disease
#20
Shanshan Shi, Xiuchun Zhang, M Alejandra Mandel, Peng Zhang, Yuliang Zhang, Morag Ferguson, Teddy Amuge, Steve Rounsley, Zhixin Liu, Zhongguo Xiong
Cassava (Manihot esculenta) is an important tropical subsistence crop that is severely affected by cassava brown streak disease (CBSD) in East Africa. The disease is caused by Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). Both have a (+)-sense single-stranded RNA genome with a 5' covalently-linked viral protein, which functionally resembles the cap structure of mRNA, binds to eukaryotic translation initiation factor 4E (eIF4E) or its analogues, and then enable the translation of viral genomic RNA in host cells...
2017: PloS One
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