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https://www.readbyqxmd.com/read/29345355/effects-of-antioxidants-on-apoptosis-induced-by-dasatinib-and-nilotinib-in-k562-cells
#1
Sara Damiano, Serena Montagnaro, Maria Valeria Puzio, Lorella Severino, Ugo Pagnini, Marcella Barbarino, Daniele Cesari, Antonio Giordano, Salvatore Florio, Roberto Ciarcia
In clinical practice for the treatment of chronic myeloid leukemia, second generation of tyrosine kinase inhibitors such as Nilotinib (NIL) specific and potent inhibitor of the BCR/ABL kinase and Dasatinib (DAS) a inhibitor of BCR/ABL and Src family kinase were developed to clinically overcome imatinib resistance. In this study we wanted to test the ability of some antioxidants such Resveratrol (RES) or a new recombinant mitochondrial manganese containing superoxide dismutase (rMnSOD) or δ-tocotrienol (δ-TOCO) to interact with DAS and NIL on viability, reactive oxygen species (ROS) production, lipid peroxidation and apoptosis...
January 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29338035/genome-wide-identification-of-wheat-and-brachypodium-type-one-protein-phosphatases-and-functional-characterization-of-durum-wheat-tdpp1a
#2
Mariem Bradai, Habib Mahjoubi, Andrea Chini, Marie-Edith Chabouté, Moez Hanin, Chantal Ebel
Reversible phosphorylation is an essential mechanism regulating signal transduction during development and environmental stress responses. An important number of dephosphorylation events in the cell are catalyzed by type one protein phosphatases (PP1), which catalytic activity is driven by the binding of regulatory proteins that control their substrate specificity or subcellular localization. Plants harbor several PP1 isoforms accounting for large functional redundancies. While animal PP1s were reported to play relevant roles in controlling multiple cellular processes, plant orthologs remain poorly studied...
2018: PloS One
https://www.readbyqxmd.com/read/29329077/nano-hydroxyapatite-blasted-titanium-surface-creates-a-biointerface-able-to-govern-src-dependent-osteoblast-metabolism-as-prerequisite-to-ecm-remodeling
#3
Célio J C Fernandes, Fábio Bezerra, Marcel R Ferreira, Amanda F C Andrade, Thais Silva Pinto, Willian F Zambuzzi
Over the last several years, we have focused on the importance of intracellular signaling pathways in dynamically governing the biointerface between pre-osteoblast and surface of biomaterial. Thus, this study investigates the molecular hallmarks involved in the pre-osteoblast relationship with different topography considering Machined (Mc), Dual Acid-Etching (DAE), and nano hydroxyapatite-blasted (nHA) groups. There was substantial differences in topography of titanium surface, considering Atomic Force Microscopy and water contact angle (Mc = 81...
December 28, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29311589/characterization-of-the-interactions-between-inhibitor-1-and-recombinant-pp1-by-nmr-spectroscopy
#4
Chu-Ting Liang, Yu-Shan Lin, Yi-Choang Huang, Hsien-Lu Huang, Jia-Qian Yang, Tsung-Hsien Wu, Chi-Fon Chang, Shing-Jong Huang, Hsien-Bin Huang, Ta-Hsien Lin
Inhibitor-1 is converted into a potent inhibitor of native protein phosphatase-1 (PP1) when Thr35 is phosphorylated by cAMP-dependent protein kinase (PKA). However, PKA-phosphorylated form of inhibitor-1 displayed a weak activity in inhibition of recombinant PP1. The mechanism for the impaired activity of PKA-phosphorylated inhibitor-1 toward inhibition of recombinant PP1 remained elusive. By using NMR spectroscopy in combination with site-directed mutagenesis and inhibitory assay, we found that the interaction between recombinant PP1 and the consensus PP1-binding motif of PKA-thiophosphorylated form of inhibitor-1 was unexpectedly weak...
January 8, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29311130/mras-a-close-but-understudied-member-of-the-ras-family
#5
Lucy C Young, Pablo Rodriguez-Viciana
MRAS is the closest relative to the classical RAS oncoproteins and shares most regulatory and effector interactions. However, it also has unique functions, including its ability to function as a phosphatase regulatory subunit when in complex with SHOC2 and protein phosphatase 1 (PP1). This phosphatase complex regulates a crucial step in the activation cycle of RAF kinases and provides a key coordinate input required for efficient ERK pathway activation and transformation by RAS. MRAS mutations rarely occur in cancer but deregulated expression may play a role in tumorigenesis in some settings...
January 8, 2018: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/29302216/functional-identification-of-protein-phosphatase-1-binding-consensus-residues-in-nbce1-b
#6
Kyu Pil Lee, Hyun Jin Kim, Dongki Yang
Protein phosphatase 1 (PP1) is involved in various signal transduction mechanisms as an extensive regulator. The PP1 catalytic subunit (PP1c) recognizes and binds to PP1-binding consensus residues (FxxR/KxR/K) in NBCe1-B. Consequently, we focused on identifying the function of the PP1-binding consensus residue, 922FMDRLK927, in NBCe1-B. Using site-directed mutagenesis and co-immunoprecipitation assays, we revealed that in cases where the residues were substituted (F922A, R925A, and K927A) or deleted (deletion of amino acids 922-927), NBCe1-B mutants inhibited PP1 binding to NBCe1-B...
January 2018: Korean Journal of Physiology & Pharmacology
https://www.readbyqxmd.com/read/29299971/the-role-of-the-fas-fasl-signaling-pathway-in-environmental-toxicant-induced-testicular-cell-apoptosis-an-update
#7
Mei Wang, Ping Su
The Fas/FasL signaling pathway is one of the major pathways that regulate apoptosis. Increasing studies have shown that the activation of the Fas/FasL signaling pathway is closely associated with testicular cell apoptosis. However, the mechanism involved is still unclear. We discuss recent findings regarding the molecular mechanisms by which environmental toxicants induce testicular pathology via Fas/FasL signaling. These findings suggest that Fas/FasL signaling is employed to impact the sensitivity (a response to external factors) of germ cells, disrupt steroidogenic hormone and cytokine metabolism mediated by Sertoli cells, and elicit the activation of NFAT (nuclear factor of activated T-cells) in Leydig cell apoptosis...
January 4, 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29288365/methylphenidate-disrupts-cytoskeletal-homeostasis-and-reduces-membrane-associated-lipid-content-in-juvenile-rat-hippocampus
#8
Felipe Schmitz, Paula Pierozan, Helena Biasibetti-Brendler, Fernanda Silva Ferreira, Fernanda Dos Santos Petry, Vera Maria Treis Trindade, Regina Pessoa-Pureur, Angela T S Wyse
Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 44th day of age. Results showed that MPH provoked hypophosphorylation of glial fibrillary acidic protein (GFAP) and reduced its immunocontent...
December 29, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/29285244/coordinated-downregulation-of-spinophilin-and-the-catalytic-subunits-of-pp1-ppp1ca-b-c-contributes-to-a-worse-prognosis-in-lung-cancer
#9
Eva M Verdugo-Sivianes, Lola Navas, Sonia Molina-Pinelo, Irene Ferrer, Alvaro Quintanal-Villalonga, Javier Peinado, Jose M Garcia-Heredia, Blanca Felipe-Abrio, Sandra Muñoz-Galvan, Juan J Marin, Luis Montuenga, Luis Paz-Ares, Amancio Carnero
The scaffold protein Spinophilin (Spinophilin, PPP1R9B) is one of the regulatory subunits of phosphatase-1 (PP1), directing it to distinct subcellular locations and targets. The loss of Spinophilin reduces PP1 targeting to pRb, thereby maintaining higher levels of phosphorylated pRb. Spinophilin is absent or reduced in approximately 40% of human lung tumors, correlating with the malignant grade. However, little is known about the relevance of the coordinated activity or presence of Spinophilin and its reported catalytic partners in the prognosis of lung cancer...
December 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/29273751/excitotoxic-inactivation-of-constitutive-oxidative-stress-detoxification-pathway-in-neurons-can-be-rescued-by-pkd1
#10
Julia Pose-Utrilla, Lucía García-Guerra, Ana Del Puerto, Abraham Martín, Jerónimo Jurado-Arjona, Noelia S De León-Reyes, Andrea Gamir-Morralla, Álvaro Sebastián Serrano, Mónica García-Gallo, Leonor Kremer, Jens Fielitz, Christofer Ireson, Mª José Pérez-Álvarez, Isidro Ferrer, Félix Hernández, Jesús Ávila, Marina Lasa, Miguel R Campanero, Teresa Iglesias
Excitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway...
December 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/29230547/novel-fluorochromes-label-tonoplast-in-living-plant-cells-and-reveal-changes-in-vacuolar-organization-after-treatment-with-protein-phosphatase-inhibitors
#11
Miklós Nagy, Sándor Kéki, Dávid Rácz, Jaideep Mathur, György Vereb, Tamás Garda, Márta M-Hamvas, François Chaumont, Károly Bóka, Béla Böddi, Csongor Freytag, Gábor Vasas, Csaba Máthé
The recently synthesized isocyanonaphtalene derivatives ACAIN and CACAIN are fluorochromes excitable at wavelengths of around 366 nm and bind cysteine-rich proteins with hydrophobic motifs. We show that these compounds preferentially label tonoplasts in living Arabidopsis and tobacco (Nicotiana tabacum SR1) cells. ACAIN-labeled membranes co-localized with the GFP signal in plants expressing GFP-δ-TIP (TIP2;1) (a tonoplast aquaporin) fusion protein. ACAIN preserved the dynamics of vacuolar structures. tip2;1 and triple tip1;1-tip1;2-tip2;1 knockout mutants showed weaker ACAIN signal in tonoplasts...
December 12, 2017: Protoplasma
https://www.readbyqxmd.com/read/29222185/p37-ubxn2b-regulates-spindle-orientation-by-limiting-cortical-numa-recruitment-via-pp1-repo-man
#12
Byung Ho Lee, Francoise Schwager, Patrick Meraldi, Monica Gotta
Spindle orientation determines the axis of division and is crucial for cell fate, tissue morphogenesis, and the development of an organism. In animal cells, spindle orientation is regulated by the conserved Gαi-LGN-NuMA complex, which targets the force generator dynein-dynactin to the cortex. In this study, we show that p37/UBXN2B, a cofactor of the p97 AAA ATPase, regulates spindle orientation in mammalian cells by limiting the levels of cortical NuMA. p37 controls cortical NuMA levels via the phosphatase PP1 and its regulatory subunit Repo-Man, but it acts independently of Gαi, the kinase Aurora A, and the phosphatase PP2A...
December 8, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/29212034/gadd34-function-in-protein-trafficking-promotes-adaptation-to-hyperosmotic-stress-in-human-corneal-cells
#13
Dawid Krokowski, Bo-Jhih Guan, Jing Wu, Yuke Zheng, Padmanabhan P Pattabiraman, Raul Jobava, Xing-Huang Gao, Xiao-Jing Di, Martin D Snider, Ting-Wei Mu, Shijie Liu, Brian Storrie, Eric Pearlman, Anna Blumental-Perry, Maria Hatzoglou
GADD34, a stress-induced regulatory subunit of the phosphatase PP1, is known to function in hyperosmotic stress through its well-known role in the integrated stress response (ISR) pathway. Adaptation to hyperosmotic stress is important for the health of corneal epithelial cells exposed to changes in extracellular osmolarity, with maladaptation leading to dry eye syndrome. This adaptation includes induction of SNAT2, an endoplasmic reticulum (ER)-Golgi-processed protein, which helps to reverse the stress-induced loss of cell volume and promote homeostasis through amino acid uptake...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29183804/modulation-of-nnosser852-phosphorylation-and-translocation-by-pka-pp1-pathway-in-endothelial-cells
#14
Juliana M Navia-Pelaez, Gianne P Campos-Mota, Jessica C Araujo-Souza, Nikos Stergiopulos, Luciano S A Capettini
Neuronal nitric oxide synthase (nNOS) is now considered an important player in vascular function. It has a protective role in atherosclerosis and hypertension. However, despite its importance, little is known about the mechanisms that regulate its activity in vascular cells. Here we explore the mechanisms by which nNOS is activated in endothelium. We evaluated aorta relaxation response and phosphorylation of nNOS during protein phosphatases 1 and 2 (PP1 and PP2) inhibition, in eNOS silenced mice. PP1 translocation and interaction between the nuclear inhibitor of PP1 (NIPP1) and PP1 was evaluated in endothelial EA...
November 25, 2017: Nitric Oxide: Biology and Chemistry
https://www.readbyqxmd.com/read/29163047/biphasic-regulation-of-caveolin-1-gene-expression-by-fluoxetine-in-astrocytes-opposite-effects-of-pi3k-akt-and-mapk-erk-signaling-pathways-on-c-fos
#15
Baoman Li, Shu Jia, Tingting Yue, Li Yang, Chen Huang, Alexej Verkhratsky, Liang Peng
Previously, we reported that fluoxetine acts on 5-HT2B receptor and induces epidermal growth factor receptor (EGFR) transactivation in astrocytes. Recently, we have found that chronic treatment with fluoxetine regulates Caveolin-1 (Cav-1)/PTEN/PI3K/AKT/glycogen synthase kinase 3β (GSK-3β) signaling pathway and glycogen content in primary cultures of astrocytes with bi-phasic concentration dependence. At low concentrations fluoxetine down-regulates Cav-1 gene expression, decreases membrane content of PTEN, increases PI3K activity and increases phosphorylation of GSK-3β and increases its activity; at high concentrations fluoxetine acts on PTEN/PI3K/AKT/GSK-3β in an inverse fashion...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/29158294/the-actin-binding-protein-ppp1r18-regulates-maturation-actin-organization-and-bone-resorption-activity-of-osteoclasts
#16
Takuma Matsubara, Shoichiro Kokabu, Chihiro Nakatomi, Masayuki Kinbara, Toshihiro Maeda, Mitsuhiro Yoshizawa, Hisataka Yasuda, Teruko Takano-Yamamoto, Roland Baron, Eijiro Jimi
Osteoclasts resorb bone by attaching on the bone matrix and forming a sealing zone. In Src-deficient mice, osteoclasts cannot form the actin ring, a characteristic actin structure that seals the resorbed area, and hardly resorb any bone as a result. However, the molecular mechanism underlying the role of Src in the regulation and organization of the actin ring is still unclear. We identified an actin regulatory protein, protein phosphatase 1 regulatory subunit 18 (PPP1r18), as an Src-binding protein in an Src-, Yes-, and Fyn-deficient fibroblast (SYF) cell line overexpressing a constitutively active form of Src...
November 20, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29156132/the-pp1-tautomycetin-complex-reveals-a-path-towards-the-development-of-pp1-specific-inhibitors
#17
Meng S Choy, Mark Swingle, Brandon D'Arcy, Kevin Abney, Scott F Rusin, Arminja N Kettenbach, Rebecca Page, Richard E Honkanen, Wolfgang Peti
Selective inhibitors for each serine/threonine phosphatase (PPP) are essential to investigate the biological actions of PPPs and to guide drug development. Although multiple organisms (cyanobacteria, dinoflagellates, beetles, etc.) produce natural toxins that bind and inhibit the active sites of PPPs, they are largely non-selective, typically inhibiting one or more family members with equal potencies. Thus, the use of these toxins as chemical tools to study the relationship between individual PPPs and their biological substrates, and how disruptions in these relationships contributes to human disease, is severely limited...
November 20, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29141582/a-novel-interaction-between-kinase-activities-in-regulation-of-cilia-formation
#18
Nicole DeVaul, Katerina Koloustroubis, Rong Wang, Ann O Sperry
BACKGROUND: The primary cilium is an extension of the cell membrane that encloses a microtubule-based axoneme. Primary cilia are essential for transmission of environmental cues that determine cell fate. Disruption of primary cilia function is the molecular basis of numerous developmental disorders. Despite their biological importance, the mechanisms governing their assembly and disassembly are just beginning to be understood. Cilia growth and disassembly are essential events when cells exit and reenter into the cell cycle...
November 15, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/29140585/timap-the-versatile-protein-phosphatase-1-regulator-in-endothelial-cells
#19
REVIEW
Anita Boratkó, Csilla Csortos
Transforming growth factor (TGF)-β inhibited membrane associated protein, TIMAP, is the member of the myosin phosphatase targeting protein (MYPT) family of protein phosphatase 1 (PP1) regulatory subunits. The N-terminal part of TIMAP has a typical MYPT family structure with a sequence element called MyPhone (myosin phosphatase N-terminal element), a putative bipartite nuclear localization signal, a PP1 catalytic subunit binding motif, and five ankyrin repeats. The C-terminal half of TIMAP is intrinsically disordered, but ends with a functional CAAX box for lipid modification which allows localization of TIMAP at the plasma membrane...
November 15, 2017: IUBMB Life
https://www.readbyqxmd.com/read/29126937/coccinia-indica-agglutinin-a-17kda-pp2-like-phloem-lectin-affinity-purification-primary-structure-and-formation-of-self-assembled-filaments
#20
Kishore Babu Bobbili, Gottfried Pohlentz, Akkaladevi Narahari, Kaushal Sharma, A Surolia, Michael Mormann, Musti J Swamy
Phloem protein-2 (PP2) is an abundant soluble protein in the sieve elements in plants. Its lectin property was reported in various species. The primary structure of PP2 from Coccinia indica (Coccinia indica agglutinin, CIA17), determined by mass spectrometry, shows extensive homology with PP2 super family phloem lectins. Analysis of mass spectrometric data indicated the presence of 16 potential allelic variants of CIA17 with insignificant divergence in the primary structure. The primary structure contains an intramolecular disulfide bridge between Cys-34 and Cys-51, which is conserved across various cucurbit species and hence likely to be important for carbohydrate binding...
November 7, 2017: International Journal of Biological Macromolecules
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