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https://www.readbyqxmd.com/read/29054108/increase-in-pro-apoptotic-activity-of-inhibitory-pas-domain-protein-via-phosphorylation-by-mk2
#1
Shuya Kasai, Mary Jane Elizabeth Richardson, Satoru Torii, Ken-Ichi Yasumoto, Hiroki Shima, Kazuhiko Igarashi, Ken Itoh, Kazuhiro Sogawa, Kazutaka Murayama
Inhibitory PAS domain protein (IPAS) is a bifunctional protein that downregulates hypoxic gene expression and exerts pro-apoptotic activity by preventing pro-survival activity of Bcl-xL and its related factors. Pro-apoptotic activity of IPAS is attenuated by the activation of the PINK1-Parkin pathway, and involved in neuronal degeneration in an experimental mouse model of Parkinson's disease. The current study shows that phosphorylation of IPAS at Ser184 by MAPK-activated protein kinase 2 (MK2 or MAPKAPK2) enhances the pro-apoptotic function of IPAS...
October 20, 2017: FEBS Journal
https://www.readbyqxmd.com/read/29054039/control-of-brain-energy-supply-by-astrocytes
#2
REVIEW
Ross Nortley, David Attwell
Astrocytes form an anatomical bridge between the vasculature and neuronal synapses. Recent work suggests that they play a key role in regulating brain energy supply by increasing blood flow to regions where neurons are active, and setting the baseline level of blood flow. Controversy persists over whether lactate derived from astrocyte glycolysis is used to power oxidative phosphorylation in neurons, but astrocytes sustain neuronal ATP production by recycling neurotransmitter glutamate that would otherwise need to be resynthesised from glucose, and by providing a short-term energy store in the form of glycogen that can be mobilised when neurons are active...
October 17, 2017: Current Opinion in Neurobiology
https://www.readbyqxmd.com/read/29053961/maturation-of-xenopus-laevis-oocytes-under-cadmium-and-lead-exposures-cell-biology-investigations
#3
Sylvain Slaby, Julie Hanotel, Guillaume Marchand, Arlette Lescuyer, Jean-François Bodart, Alain Leprêtre, Sébastien Lemière, Matthieu Marin
Since amphibians are recognised as good models to assess the quality of environments, only few studies have dealt with the impacts of chemical contaminants on their gametes, while toxic effects at this stage will alter all the next steps of their life cycle. Therefore, we propose to investigate the oocyte maturation of Xenopus laevis in cadmium- and lead-contaminated conditions. The impacts of cadmium and lead ions were explored on events involved in the hormone-dependent process of maturation. In time-course experiments, cadmium, at the highest concentration, delayed and prevented the germinal vesicle breakdown...
October 16, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29053960/a-general-strategy-for-discovery-of-inhibitors-and-activators-of-ring-and-u-box-e3-ligases-with-ubiquitin-variants
#4
Mads Gabrielsen, Lori Buetow, Mark A Nakasone, Syed Feroj Ahmed, Gary J Sibbet, Brian O Smith, Wei Zhang, Sachdev S Sidhu, Danny T Huang
RING and U-box E3 ubiquitin ligases regulate diverse eukaryotic processes and have been implicated in numerous diseases, but targeting these enzymes remains a major challenge. We report the development of three ubiquitin variants (UbVs), each binding selectively to the RING or U-box domain of a distinct E3 ligase: monomeric UBE4B, phosphorylated active CBL, or dimeric XIAP. Structural and biochemical analyses revealed that UbVs specifically inhibited the activity of UBE4B or phosphorylated CBL by blocking the E2∼Ub binding site...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29053957/cdk4-phosphorylates-ampk%C3%AE-2-to-inhibit-its-activity-and-repress-fatty-acid-oxidation
#5
Isabel C Lopez-Mejia, Sylviane Lagarrigue, Albert Giralt, Laia Martinez-Carreres, Nadège Zanou, Pierre-Damien Denechaud, Judit Castillo-Armengol, Carine Chavey, Meritxell Orpinell, Brigitte Delacuisine, Anita Nasrallah, Caterina Collodet, Lianjun Zhang, Benoît Viollet, D Grahame Hardie, Lluis Fajas
The roles of CDK4 in the cell cycle have been extensively studied, but less is known about the mechanisms underlying the metabolic regulation by CDK4. Here, we report that CDK4 promotes anaerobic glycolysis and represses fatty acid oxidation in mouse embryonic fibroblasts (MEFs) by targeting the AMP-activated protein kinase (AMPK). We also show that fatty acid oxidation (FAO) is specifically induced by AMPK complexes containing the α2 subunit. Moreover, we report that CDK4 represses FAO through direct phosphorylation and inhibition of AMPKα2...
October 19, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29053918/active-site-interactions-impact-phosphoryl-transfer-during-replication-of-damaged-and-undamaged-dna-by-escherichia-coli-dna-polymerase-i
#6
A S Prakasha Gowda, Thomas E Spratt
Replicative DNA polymerases are able to discriminate between very similar substrates with high accuracy. One mechanism by which Escherichia coli DNA polymerase I checks for Watson-Crick geometry is through a hydrogen bonding fork between Arg668 and the incoming dNTP and the minor groove of the primer terminus. The importance of the Arg-fork was examined by disrupting it with either a guanine to 3-deazaguanine substitution at the primer terminus or the use of a carbocyclic deoxyribose analog of dUTP. Using thio-substituted dNTPs and differential quench techniques, we determined that when the Arg-fork was disrupted, the rate limiting step changed from a conformational change to phosphodiester bond formation...
October 20, 2017: Chemical Research in Toxicology
https://www.readbyqxmd.com/read/29053748/treatment-with-the-nr4a1-agonist-cytosporone-b-controls-influenza-virus-infection-and-improves-pulmonary-function-in-infected-mice
#7
Benoit Egarnes, Marie-Renée Blanchet, Jean Gosselin
The transcription factor NR4A1 has emerged as a pivotal regulator of the inflammatory response and immune homeostasis. Although contribution of NR4A1 in the innate immune response has been demonstrated, its role in host defense against viral infection remains to be investigated. In the present study, we show that administration of cytosporone B (Csn-B), a specific agonist of NR4A1, to mice infected with influenza virus (IAV) reduces lung viral loads and improves pulmonary function. Our results demonstrate that administration of Csn-B to naive mice leads to a modest production of type 1 IFN...
2017: PloS One
https://www.readbyqxmd.com/read/29053747/establishment-of-pten-knockout-medaka-with-transcription-activator-like-effector-nucleases-talens-as-a-model-of-pten-deficiency-disease
#8
Yuriko Matsuzaki, Tetsushi Sakuma, Takashi Yamamoto, Hideyuki Saya
Phosphatase and tensin homolog (PTEN) is a lipid and protein phosphatase that antagonizes signaling by the phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway. The PTEN gene is a major tumor suppressor, with mutations of this gene occurring frequently in tumors of humans and mice. We have now developed mutant medaka deficient in PTEN with the use of transcription activator-like effector nuclease (TALEN) technology. Medaka possesses two pten genes, ptena and ptenb, similar to zebrafish. We established 16 ptena mutant lines and two ptenb mutant lines...
2017: PloS One
https://www.readbyqxmd.com/read/29053745/impact-of-the-structural-integrity-of-the-three-way-junction-of-adenovirus-vai-rna-on-pkr-inhibition
#9
Edis Dzananovic, Astha, Grzegorz Chojnowski, Soumya Deo, Evan P Booy, Pauline Padilla-Meier, Kevin McEleney, Janusz M Bujnicki, Trushar R Patel, Sean A McKenna
Highly structured RNA derived from viral genomes is a key cellular indicator of viral infection. In response, cells produce the interferon inducible RNA-dependent protein kinase (PKR) that, when bound to viral dsRNA, phosphorylates eukaryotic initiation factor 2α and attenuates viral protein translation. Adenovirus can evade this line of defence through transcription of a non-coding RNA, VAI, an inhibitor of PKR. VAI consists of three base-paired regions that meet at a three-way junction; an apical stem responsible for the interaction with PKR, a central stem required for inhibition, and a terminal stem...
2017: PloS One
https://www.readbyqxmd.com/read/29053678/assay-for-phosphorylation-and-microtubule-binding-along-with-localization-of-tau-protein-in-colorectal-cancer-cells
#10
Md Nazmul Huda, Erdenedolgor Erdene-Ochir, Cheol-Ho Pan
The microtubule-associated protein tau is a neuronal protein that localizes mostly in axons. Generally tau is essential for normal neuronal functioning because it is involved in microtubule assembly and stabilization. Besides neurons, tau is expressed in human breast, prostate, gastric, colorectal, and pancreatic cancers where it shows nearly similar structure and exerts similar functions as the neuronal tau. The amount of tau and its phosphorylation can change its function as a stabilizer of microtubules, and lead to the development of paired helical filaments in different neurodegenerative disorders, such as Alzheimer's disease...
October 10, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29053643/genome-wide-identification-and-analysis-of-mapk-and-mapkk-gene-families-in-bread-wheat-triticum-aestivum-l
#11
Haoshuang Zhan, Hong Yue, Xian Zhao, Meng Wang, Weining Song, Xiaojun Nie
The mitogen-activated protein kinase (MAPK) cascade is a universal signal transduction module that plays a vital role in regulating growth and development, as well as environmental stress responses in plants. Wheat is one of the most important crops worldwide. Although the MAPK kinase kinase (MAP3K) family in wheat has been investigated, the MAPK and MAPK kinase (MAP2K) gene families remain unknown at present. Here, 54 MAPK and 18 MAPKK genes were identified in wheat using recent genomic information. Phylogenetic analysis of Triticum aestivum L...
October 20, 2017: Genes
https://www.readbyqxmd.com/read/29053621/isoproterenol-increases-rankl-expression-in-a-atf4-nfatc1-dependent-manner-in-mouse-osteoblastic-cells
#12
Kyunghwa Baek, Hyun-Jung Park, Jeong-Hwa Baek, Hyung-Ryong Kim
Sympathetic nervous system stimulation-induced β-adrenergic signal transduction is known to induce bone loss and increase of osteoclast activity. Although isoproterenol, a nonspecific β-adrenergic receptor agonist, has been shown to increase receptor activator of NF-κB ligand (RANKL), the details of the regulatory mechanisms remain unclear. In the present study, we investigated the role of the nuclear factor of activated T-cells (NFAT) in isoproterenol-induced RANKL expression in C2C12 and in primary cultured mouse calvarial cells...
October 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29053582/zinc-supplementation-improves-glucose-homeostasis-in-high-fat-fed-mice-by-enhancing-pancreatic-%C3%AE-cell-function
#13
Vinícius Cooper-Capetini, Diogo Antonio Alves de Vasconcelos, Amanda Roque Martins, Sandro Massao Hirabara, José Donato, Angelo Rafael Carpinelli, Fernando Abdulkader
Zinc is an essential component of the insulin granule and it possibly modulates insulin secretion and signaling. Since insulin resistance is a hallmark in the development of type 2 diabetes mellitus, this study aimed at investigating if zinc supplementation is able to improve glucose tolerance and β-cell function in a model of insulin resistance. Male C57BL/6 mice were distributed in four groups according to the diet: normal fat (NF); normal fat supplemented with ZnCl₂ (NFZ); high-fat (HF); and, high-fat chow supplemented with ZnCl₂ (HFZ)...
October 20, 2017: Nutrients
https://www.readbyqxmd.com/read/29053518/role-of-homeodomain-interacting-protein-kinase-2-in-the-pathogenesis-of-tissue-fibrosis-in-keloid-derived-keratinocytes
#14
Yi-Xuan Zhao, Guo-You Zhang, An-Yuan Wang, Ya-Hong Chen, Da-Mu Lin, Qing-Feng Li
Epithelial-mesenchymal transition (EMT) plays a critical role in fibrotic keloid formation, which is characterized by excessive collagen and extracellular matrix synthesis and deposition. Growing evidence suggests that the serine/threonine kinase homeodomain-interacting protein kinase 2 (HIPK2) acts upstream of several major fibrosis signaling pathways; however, the role of HIPK2 in the keloid fibrogenesis remains unknown. In the current study, we investigated the roles of HIPK2 in the pathogenesis of keloids...
October 19, 2017: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/29053414/perk-phosphorylated-eif2%C3%AE-pathway-suppresses-tumor-metastasis-through-downregulating-expression-of-programmed-death-ligand-1-and-cxcl5-in-triple-negative-breast-cancer
#15
Weiwei Zou, Yu Bai, Xilong Wang, Kai Cheng, Hongguang Sun, Guoqiang Zhang, Xiaohong Wang, Zhenlin Yang
Endoplasmic reticulum (ER) stress has been reported to be associated with metastasis in many malignant tumors. PKR-like ER kinase-phosphorylated eukaryotic translation initiation factor 2α (PERK-p-eIF2α) pathway is one of the three main signal pathways in ER stress, however, its mechanism in regulating breast cancer (BC) relapse or metastasis was still not completely understood. Besides, drug resistance was an important factor influencing the effect of tumor treatment and whether PERK-p-eIF2α pathway was involved in the drug resistance to BC treatment also needs to be explored...
October 2017: Cancer Biotherapy & Radiopharmaceuticals
https://www.readbyqxmd.com/read/29053406/super-resolution-nanoscopy-imaging-applied-to-dna-double-strand-breaks
#16
Sofia D'Abrantes, Sarah Gratton, Pamela Reynolds, Verena Kriechbaumer, Joseph McKenna, Stephen Barnard, Dave Clarke, Stanley W Botchway
Genomic deoxyribonucleic acid (DNA) is continuously being damaged by endogenous processes such as metabolism or by exogenous events such as radiation. The specific phosphorylation of histone H2AX on serine residue 139, described as γ-H2AX, is an excellent indicator or marker of DNA double-strand breaks (DSBs). The yield of γ-H2AX (foci) is shown to have some correlation with the dose of radiation or other DSB-causing agents. However, there is some discrepancy in the DNA DSB foci yield among imaging and other methods such as gel electrophoresis...
October 20, 2017: Radiation Research
https://www.readbyqxmd.com/read/29053396/embryonic-stem-cell-secreted-factors-decrease-invasiveness-of-triple-negative-breast-cancer-cells-through-regulome-modulation
#17
Elizabeth Tarasewicz, Robert S Oakes, Misael O Aviles, Joelle Straehla, Kathryn M Chilton, Joseph T Decker, Jia Wu, Lonnie D Shea, Jacqueline S Jeruss
Stem cell microenvironments decrease the invasiveness of cancer cells, and elucidating the mechanisms associated with disease regression could further the development of targeted therapies for aggressive cancer subtypes. To this end, we applied an emerging technology, TRanscriptional Activity CEll aRray (TRACER), to investigate the reprogramming of triple-negative breast cancer (TNBC) cells in conditions that promoted a less aggressive phenotype. The repressive environment was established through exposure to mouse embryonic stem cell conditioned media (mESC CM)...
October 20, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/29052917/posttranslational-modifications-as-key-regulators-of-apicomplexan-biology-insights-from-proteome-wide-studies
#18
REVIEW
Rama R Yakubu, Louis M Weiss, Natalie C Silmon de Monerri
Parasites of the Apicomplexa phylum, such as Plasmodium spp. and Toxoplasma gondii., undergo complex life cycles involving multiple stages with distinct biology and morphologies. Posttranslational modifications (PTMs), such as phosphorylation, acetylation and glycosylation, regulate numerous cellular processes, playing a role in every aspect of cell biology. PTMs can occur on proteins at any time in their lifespan and through alterations of target protein activity, localization, protein-protein interactions, among other functions, dramatically increase proteome diversity and complexity...
October 20, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29052909/allosteric-control-of-a-bacterial-stress-response-system-by-an-anti-%C3%AF-factor
#19
Justin L Luebke, Daniel S Eaton, Joseph R Sachleben, Sean Crosson
Bacterial signal transduction systems commonly use receiver (REC) domains, which regulate adaptive responses to the environment as a function of their phosphorylation state. REC domains control cell physiology through diverse mechanisms, many of which remain understudied. We have defined structural features that underlie activation of the multi-domain REC protein, PhyR, which functions as an anti-anti-σ factor and regulates transcription of genes required for stress adaptation and host-microbe interactions in Alphaproteobacteria...
October 20, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/29052798/curcumin-pretreatment-prevents-hydrogen-peroxide-induced-oxidative-stress-through-enhanced-mitochondrial-function-and-deactivation-of-akt-erk-signaling-pathways-in-rat-bone-marrow-mesenchymal-stem-cells
#20
Xujie Wang, Jianxin Gao, Yunchuan Wang, Bin Zhao, Yijie Zhang, Fu Han, Zhao Zheng, Dahai Hu
Bone marrow mesenchymal stem cells (BMSCs)-based therapy has emerged as a desirable modality for the treatment of tissue injury with promising therapeutic effects; however, low survival rate of transplanted cells due to harsh microenvironment with hypoxia and oxidative stress results in hampered therapeutic benefits of this therapy. Curcumin, a natural bioactive product, is a dietary component which has gained increasing attention owing to its beneficial health properties. Here, we reported the protective effects of curcumin pretreatment on BMSCs injury induced by hydrogen peroxide (H2O2), which was used as ROS source of oxidative stress in vitro...
October 20, 2017: Molecular and Cellular Biochemistry
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