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https://www.readbyqxmd.com/read/28092675/unbalancing-p53-mdm2-igf-1r-axis-by-mdm2-activation-restrains-the-igf-1-dependent-invasive-phenotype-of-skin-melanoma
#1
C Worrall, N Suleymanova, C Crudden, I Trocoli Drakensjö, E Candrea, D Nedelcu, S-I Takahashi, L Girnita, A Girnita
Melanoma tumors usually retain wild-type p53; however, its tumor-suppressor activity is functionally disabled, most commonly through an inactivating interaction with mouse double-minute 2 homolog (Mdm2), indicating p53 release from this complex as a potential therapeutic approach. P53 and the tumor-promoter insulin-like growth factor type 1 receptor (IGF-1R) compete as substrates for the E3 ubiquitin ligase Mdm2, making their relative abundance intricately linked. Hence we investigated the effects of pharmacological Mdm2 release from the Mdm2/p53 complex on the expression and function of the IGF-1R...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28091789/comparative-investigation-on-a-hexane-degrading-strain-with-different-cell-surface-hydrophobicities-mediated-by-starch-and-chitosan
#2
Dong-Zhi Chen, Ning-Xin Jiang, Jie-Xu Ye, Zhuo-Wei Cheng, Shi-Han Zhang, Jian-Meng Chen
Bioremediation usually exhibits low removal efficiency toward hexane because of poor water solubility, which limits the mass transfer rate between the substrate and microorganism. This work aimed to enhance the hexane degradation rate by increasing cell surface hydrophobicity (CSH) of the degrader, Pseudomonas mendocina NX-1. The CSH of P. mendocina NX-1 was manipulated by treatment with starch and chitosan solution of varied concentrations, reaching a maximum hydrophobicity of 52%. The biodegradation of hexane conformed to the Haldane inhibition model, and the maximum degradation rate (ν max) of the cells with 52% CSH was 0...
January 14, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28091708/the-effect-of-motor-overflow-on-bimanual-asymmetric-force-coordination
#3
David A Cunningham, Sarah M Roelle, Didier Allexandre, Kelsey A Potter-Baker, Vishwanath Sankarasubramanian, Jayme S Knutson, Guang H Yue, Andre G Machado, Ela B Plow
Motor overflow, typically described in the context of unimanual movements, refers to the natural tendency for a 'resting' limb to move during movement of the opposite limb and is thought to be influenced by inter-hemispheric interactions and intra-cortical networks within the 'resting' hemisphere. It is currently unknown, however, how motor overflow contributes to asymmetric force coordination task accuracy, referred to as bimanual interference, as there is need to generate unequal forces and corticospinal output for each limb...
January 16, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28090813/effects-of-fostriecin-on-%C3%AE-2-adrenoceptor-driven-responses-in-human-mast-cells
#4
Reza Bastan, Nahid Eskandari, Hamidrez J Ardakani, Peter T Peachell
As part of the intracellular processes leading to mast cell and basophil activation, phosphorylation of key substrates is likely to be important. These processes, mediated by phosphatases, are responsible for regulating phosphorylation. The aim of the present study was to determine effects fostriecin - a selective inhibitor of PP2A (protein phosphatase-2) - on β2-adrenoceptor-driven responses in human mast cells. Here, the effects of fostriecin (PP inhibitors) on the inhibition of histamine release from HLMC, on β-adrenoceptor-driven responses in mast cells and on desensitization were investigated...
January 16, 2017: Journal of Immunotoxicology
https://www.readbyqxmd.com/read/28089737/browplasminin-a-condensed-tannin-with-anti-plasmin-activity-isolated-from-an-aqueous-extract-of-brownea-grandiceps-jacq-flowers
#5
Betzabeth Pereira, Josmary Brazón, Mónica Rincón, Eva Vonasek
ETHNOPHARMACOLOGICAL RELEVANCE: Following Venezuelan traditional medicine, females with heavy menstrual blood loss (menorrhagia) drink Brownea grandiceps Jacq. flowers (BG) decoctions to reduce the bleeding. In a previous study, we demonstrated that BG aqueous extract (E) possesses a potent anti-fibrinolytic activity capable of inhibiting plasmin, the main serine-protease that degrades fibrin. It is widely known that plasmin inhibitors are often used as anti-fibrinolytics to reduce bleeding during surgeries with high risk of blood loss such as cardiac, liver, vascular, tooth extraction and large orthopedic procedures, as well as for menorrhagia treatments...
January 12, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28089449/transferase-versus-hydrolase-the-role-of-conformational-flexibility-in-reaction-specificity
#6
Samuel H Light, Laty A Cahoon, Kiran V Mahasenan, Mijoon Lee, Bill Boggess, Andrei S Halavaty, Shahriar Mobashery, Nancy E Freitag, Wayne F Anderson
Active in the aqueous cellular environment where a massive excess of water is perpetually present, enzymes that catalyze the transfer of an electrophile to a non-water nucleophile (transferases) require specific strategies to inhibit mechanistically related hydrolysis reactions. To identify principles that confer transferase versus hydrolase reaction specificity, we exploited two enzymes that use highly similar catalytic apparatuses to catalyze the transglycosylation (a transferase reaction) or hydrolysis of α-1,3-glucan linkages in the cyclic tetrasaccharide cycloalternan (CA)...
January 5, 2017: Structure
https://www.readbyqxmd.com/read/28088576/lid-domain-plasticity-and-lipid-flexibility-modulate-enzyme-specificity-in-human-monoacylglycerol-lipase
#7
Laura Riccardi, Jose M Arencibia, Luca Bono, Andrea Armirotti, Stefania Girotto, Marco De Vivo
Human monoacylglycerol lipase (MAGL) is a membrane-interacting enzyme that generates pro-inflammatory signaling molecules. For this reason, MAGL inhibition is a promising strategy to treat pain, cancer, and neuroinflammatory diseases. MAGL can hydrolyze monoacylglycerols bearing an acyl chain of different lengths and degrees of unsaturation, cleaving primarily the endocannabinoid 2-arachidonoylglycerol. Importantly, the enzymatic binding site of MAGL is confined by a 75-amino-acid-long, flexible cap domain, named 'lid domain', which is structurally similar to that found in several other lipases...
January 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28088531/the-effect-of-dissolved-organic-matter-on-soybean-peroxidase-mediated-removal-of-triclosan-in-water
#8
Jianhua Li, Ya Zhang, Jianbiao Peng, Xinan Wu, Shixiang Gao, Liang Mao
Dissolved organic matter (DOM) is ubiquitous in water and involved in numerous important chemical processes in aqueous systems, enabling it a unique challenge for a variety of water treatment processes. Soybean peroxidase (SBP)-based enzymatic process, as a promising treatment technique, has been successfully applied to remove pollutants in wastewaters such as coal-tar and refinery wastewater. In this study, the effect of DOM on the removal of polychlorinated aromatic antimicrobials triclosan (TCS) by SBP was investigated...
January 5, 2017: Chemosphere
https://www.readbyqxmd.com/read/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#9
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28087699/activation-of-c-abl-kinase-potentiates-the-anti-myeloma-drug-lenalidomide-by-promoting-dda1-recruitment-to-the-crl4-ubiquitin-ligase
#10
Shaobing Gao, Chenlu Geng, Tianyu Song, Xuanru Lin, Jiye Liu, Zhen Cai, Yong Cang
Cullin Ring Ligase 4 (CRL4), a complex of Cul4 and DDB1, regulates cell cycle, DNA damage repair, and chromatin replication by targeting a variety of substrates for ubiquitination. CRL4 is also hijacked by viral proteins or thalidomide-derived compounds to degrade host restriction factors. Here we report that the c-Abl non-receptor kinase phosphorylates DDB1 at residue Y316 to recruit a small regulatory protein DDA1, leading to increased substrate ubiquitination. Pharmacological inhibition or genetic ablation of the Abl-DDB1-DDA1 axis decreases the ubiquitination of CRL4 substrates, including IKZF1 and IKZF3 in lenalidomide-treated multiple myeloma cells...
January 13, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28087461/low-glucose-stress-decreases-cellular-nadh-and-mitochondrial-atp-in-colonic-epithelial-cancer-cells-influence-of-mitochondrial-substrates
#11
Magdalena L Circu, Ronald E Maloney, Tak Yee Aw
In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NADH/NAD(+)) redox homeostasis upon acute metabolic variation imposed by glucose deprivation or supplementation with mitochondrial substrates, succinate and malate/glutamate (M/G). Our results showed that low glucose caused cellular NADH/NAD(+) redox imbalance that diminished lactate dehydrogenase (LDH) activity and resulted in lower lactate contents. The concurrent activation of malic enzyme (ME) suggested a role for malate in preserving cellular pyruvate that remained unchanged at low glucose...
January 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28086938/alpha-enolase-eno1-controls-alpha-v-beta-3-integrin-expression-and-regulates-pancreatic-cancer-adhesion-invasion-and-metastasis
#12
Moitza Principe, Simone Borgoni, Mariafrancesca Cascione, Michelle Samuel Chattaragada, Sammy Ferri-Borgogno, Michela Capello, Sara Bulfamante, Jennifer Chapelle, Francesca Di Modugno, Paola Defilippi, Paola Nisticò, Paola Cappello, Chiara Riganti, Stefano Leporatti, Francesco Novelli
BACKGROUND: We have previously shown that in pancreatic ductal adenocarcinoma (PDA) cells, the glycolytic enzyme alpha-enolase (ENO1) also acts as a plasminogen receptor and promotes invasion and metastasis formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts...
January 13, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28079137/x-ray-structure-and-enzymatic-activity-profile-of-a-core-papain-like-protease-of-mers-coronavirus-with-utility-for-structure-based-drug-design
#13
Jozlyn R Clasman, Yahira M Báez-Santos, Robert C Mettelman, Amornrat O'Brien, Susan C Baker, Andrew D Mesecar
Ubiquitin-like domain 2 (Ubl2) is immediately adjacent to the N-terminus of the papain-like protease (PLpro) domain in coronavirus polyproteins, and it may play a critical role in protease regulation and stability as well as in viral infection. However, our recent cellular studies reveal that removing the Ubl2 domain from MERS PLpro has no effect on its ability to process the viral polyprotein or act as an interferon antagonist, which involves deubiquitinating and deISGylating cellular proteins. Here, we test the hypothesis that the Ubl2 domain is not required for the catalytic function of MERS PLpro in vitro...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28078567/the-c-abl-inhibitor-in-parkinson-disease
#14
REVIEW
Zhi-Hua Zhou, Yun-Fan Wu, Xue-Min Wang, Yong-Zhu Han
Parkinson's disease (PD) is an insidious onset neurodegenerative disease affecting approximately 1% of the population over the age of 65. So far available therapies for PD have only aimed at improving or alleviating symptoms, but not at slowing, preventing, and reversing the course of PD. Recently, some studies have indicated that the levels and activation of Abelson non-receptor tyrosine kinase (c-Abl, Abl1) were up-regulated in the brain tissue of patients with PD and demonstrated that c-Abl inhibitors could improve motor behavior, prevent the loss of dopamine neurons, inhibit phosphorylation of Cdk5, regulate α-synuclein phosphorylation and clearance, inhibit the tyrosine phosphorylation of parkin and decrease parkin substrate, for example, PARIS (zinc finger protein 746), AIMP2 (aminoacyl-tRNA synthetase-interacting multifunctional protein type2), FBP1 (fuse-binding protein 1), and synphilin-1...
January 11, 2017: Neurological Sciences
https://www.readbyqxmd.com/read/28077787/androgen-suppresses-protein-kinase-d1-expression-through-fibroblast-growth-factor-receptor-substrate-2-in-prostate-cancer-cells
#15
Liyong Zhang, Zhenlong Zhao, Shuping Xu, Manuj Tandon, Courtney R LaValle, Fan Deng, Q Jane Wang
In prostate cancer, androgen/androgen receptor (AR) and their downstream targets play key roles in all stages of disease progression. The protein kinase D (PKD) family, particularly PKD1, has been implicated in prostate cancer biology. Here, we examined the cross-regulation of PKD1 by androgen signaling in prostate cancer cells. Our data showed that the transcription of PKD1 was repressed by androgen in androgen-sensitive prostate cancer cells. Steroid depletion caused up regulation of PKD1 transcript and protein, an effect that was reversed by the AR agonist R1881 in a time- and concentration-dependent manner, thus identifying PKD1 as a novel androgen-repressed gene...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077617/calcineurin-the-ca2-dependent-phosphatase-regulates-rga2-a-cdc42-gtpase-activating-protein-to-modulate-pheromone-signaling
#16
Nina Ly, Martha S Cyert
Calcineurin, the conserved Ca(2+)/calmodulin-activated phosphatase, is required for viability during prolonged exposure to pheromone, and acts through multiple substrates to down regulate yeast pheromone signaling. Calcineurin regulates Dig2 and Rod1/Art4 to inhibit mating-induced gene expression and activate receptor internalization, respectively. Recent systematic approaches identified Rga2, a GTPase activating protein (GAP) for the Cdc42 Rho-type GTPase, as a calcineurin substrate. Here, we establish a physiological context for this regulation, and show that calcineurin dephosphorylates and positively regulates Rga2 during pheromone signaling...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28077572/impact-of-high-fat-diet-on-tissue-acyl-coa-and-histone-acetylation-levels
#17
Alessandro Carrer, Joshua L D Parris, Sophie Trefely, Ryan A Henry, David C Montgomery, AnnMarie Torres, John M Viola, Yin-Ming Kuo, Ian A Blair, Jordan L Meier, Andrew J Andrews, Nathaniel W Snyder, Kathryn E Wellen
Cellular metabolism dynamically regulates the epigenome via availability of the metabolite substrates of chromatin-modifying enzymes. The impact of diet on the metabolism-epigenome axis is poorly understood, but could alter gene expression and influence metabolic health. ATP-citrate lyase (ACLY) produces acetyl-CoA in the nucleus and cytosol and regulates histone acetylation levels in many cell types. Consumption of a high fat diet (HFD) results in suppression of ACLY levels in tissues such as adipose and liver, but the impact of diet on acetyl-CoA and histone acetylation in these tissues remains unknown...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28077078/transcriptomic-evidence-for-the-control-of-soybean-root-isoflavonoid-content-by-regulation-of-overlapping-phenylpropanoid-pathways
#18
Mehran Dastmalchi, Patrick Chapman, Jaeju Yu, Ryan S Austin, Sangeeta Dhaubhadel
BACKGROUND: Isoflavonoids are a class of specialized metabolites found predominantly in legumes. They play a role in signaling for symbiosis with nitrogen-fixing bacteria and inhibiting pathogen infection. RESULTS: A transcriptomic approach using soybean cultivars with high (Conrad and AC Colombe) and low (AC Glengarry and Pagoda) root isoflavonoid content was used to find elements that underlie this variation. Two genes, encoding the flavonoid-metabolizing enzymes, flavonoid 3'-hydroxylase (GmF3'H) and dihydroflavonol 4-reductase (GmDFR), had lower expression levels in high isoflavonoid cultivars...
January 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28076987/antioxidant-activity-and-cholinesterase-inhibition-studies-of-four-flavouring-herbs-from-alentejo
#19
Sílvia Arantes, Andreia Piçarra, Fátima Candeias, A Teresa Caldeira, M Rosário Martins
Essential oils (EOs) and aqueous extracts of aerial parts of four aromatic species, Calamintha nepeta, Foeniculum vulgare, Mentha spicata and Thymus mastichina, from southwest of Portugal were characterised chemically and analysed in order to evaluate their antioxidant potential and cholinesterase inhibitory activities. The main components of EOs were oxygenated monoterpenes, and aqueous extracts were rich in phenol and flavonoid compounds. EOs and aqueous extracts presented a high antioxidant potential, with ability to protect the lipid substrate, free radical scavenging and iron reducing power...
January 11, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28076454/a-broad-ph-range-and-processive-chitinase-from-a-metagenome-library
#20
S S Thimoteo, A Glogauer, H Faoro, E M de Souza, L F Huergo, B M Moerschbacher, F O Pedrosa
Chitinases are hydrolases that degrade chitin, a polymer of N-acetylglucosamine linked β(1-4) present in the exoskeleton of crustaceans, insects, nematodes and fungal cell walls. A metagenome fosmid library from a wastewater-contaminated soil was functionally screened for chitinase activity leading to the isolation and identification of a chitinase gene named metachi18A. The metachi18A gene was subcloned and overexpressed in Escherichia coli BL21 and the MetaChi18A chitinase was purified by affinity chromatography as a 6xHis-tagged fusion protein...
January 5, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
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