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https://www.readbyqxmd.com/read/28445932/high-cftr-expression-in-philadelphia-chromosome-positive-acute-leukemia-protects-and-maintains-continuous-activation-of-bcr-abl-and-related-signaling-pathways-in-combination-with-pp2a
#1
Xi Yang, Tianyou Yan, Yuping Gong, Xuehua Liu, Huaqin Sun, Wenming Xu, Chunsen Wang, Duolan Naren, Yuhuan Zheng
Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ domain, CFTR is capable of regulating other proteins, such as protein phosphatase 2A (PP2A). The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28442576/determination-of-dendritic-spine-morphology-by-the-striatin-scaffold-protein-strn4-through-interaction-with-the-phosphatase-pp2a
#2
Lianfeng Lin, Louisa Hoi-Ying Lo, Quanwei Lyu, Kwok-On Lai
Dendritic spines are heterogeneous and exist with various morphologies. Altered spine morphology might underlie the cognitive deficits in neurodevelopmental disorders such as autism, but how different subtypes of dendritic spines are selectively maintained along development is still poorly understood. Spine maturation requires spontaneous activity of N-methyl-D-aspartate (NMDA) receptor and local dendritic protein synthesis. STRN4 (also called Zinedin) belongs to the striatin family of scaffold proteins, and some of the potential striatin-interacting proteins are encoded by autism risk genes...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28441529/mps1-regulates-kinetochore-microtubule-attachment-stability-via-the-ska-complex-to-ensure-error-free-chromosome-segregation
#3
John Maciejowski, Hauke Drechsler, Kathrin Grundner-Culemann, Edward R Ballister, Jose-Antonio Rodriguez-Rodriguez, Veronica Rodriguez-Bravo, Mathew J K Jones, Emily Foley, Michael A Lampson, Henrik Daub, Andrew D McAinsh, Prasad V Jallepalli
The spindle assembly checkpoint kinase Mps1 not only inhibits anaphase but also corrects erroneous attachments that could lead to missegregation and aneuploidy. However, Mps1's error correction-relevant substrates are unknown. Using a chemically tuned kinetochore-targeting assay, we show that Mps1 destabilizes microtubule attachments (K fibers) epistatically to Aurora B, the other major error-correcting kinase. Through quantitative proteomics, we identify multiple sites of Mps1-regulated phosphorylation at the outer kinetochore...
April 24, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28439046/protein-phosphatase-2a-regulatory-subunit-b55%C3%AE-functions-in-mouse-oocyte-maturation-and-early-embryonic-development
#4
Shuang Liang, Jing Guo, Jeong-Woo Choi, Kyung-Tae Shin, Hai-Yang Wang, Yu-Jin Jo, Nam-Hyung Kim, Xiang-Shun Cui
Protein phosphatase 2A regulatory subunit B55α (PP2A-B55α) has been studied in mitosis. However, its functions in mammalian meiosis and early embryonic development remain unknown. Here, we report that PP2A-B55α is critical for mouse oocyte meiosis and preimplantation embryo development. Knockdown of PP2A-B55α in oocytes led to abnormal asymmetric division, disordered spindle dynamics, defects in chromosome congression, an increase in aneuploidy, and induction of the DNA damage response. Moreover, knockdown of PP2A-B55α in fertilized mouse zygotes impaired development to the blastocyst stage...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28438603/pp2a-catalytic-subunit-silence-by-microrna-429-activates-ampk-and-protects-osteoblastic-cells-from-dexamethasone
#5
Shiguang Guo, Caiyun Chen, Feng Ji, Li Mao, Yue Xie
Activation of AMP-activated protein kinase (AMPK) could efficiently protect osteoblasts from dexamethasone (Dex). Here, we aim to induce AMPK activation through miRNA-mediated downregulating its phosphatase, protein phosphatase 2A (PP2A). We discovered that microRNA-429 ("miR-429") targets the catalytic subunit of PP2A (PP2A-c). Significantly, expression of miR-429 downregulated PP2A-c and activated AMPK (p-AMPKα1 Thr172) in human osteoblastic cells (OB-6 and hFOB1.19 lines). Remarkably, miR-429 expression alleviated Dex-induced osteoblastic cell death and apoptosis...
April 21, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28422052/folic-acid-reduces-tau-phosphorylation-by-regulating-pp2a-methylation-in-streptozotocin-induced-diabetic-mice
#6
Miaoyan Zheng, Chen Zou, Mengyue Li, Guowei Huang, Yuxia Gao, Huan Liu
High incidence rate of Alzheimer's disease (AD) is observed in patients with type 2 diabetes. Aggregated β-amyloid (Aβ) and hyperphosphorylated tau are the hallmarks of AD. Hyperphosphorylated tau has been detected in diabetic animals as well as in diabetic patients. Folates mediate the transfer of one carbon unit, required in various biochemical reactions. The effect of folate on tau phosphorylation in diabetic models still remains unknown. In this study, we investigated the effect and mechanism of folic acid on hyperphosphorylation of tau in streptozotocin (STZ)-induced diabetic mice...
April 19, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28421341/insufficient-activation-of-akt-upon-reperfusion-because-of-its-novel-modification-by-reduced-pp2a-b55%C3%AE-contributes-to-enlargement-of-infarct-size-by-chronic-kidney-disease
#7
Toshiyuki Tobisawa, Toshiyuki Yano, Masaya Tanno, Takayuki Miki, Atsushi Kuno, Yukishige Kimura, Satoko Ishikawa, Hidemichi Kouzu, Keitaro Nishizawa, Hideaki Yoshida, Tetsuji Miura
Chronic kidney disease (CKD) increases myocardial infarct size by an unknown mechanism. Here we examined the hypothesis that impairment of protective PI3K-PDK1-Akt and/or mTORC-Akt signaling upon reperfusion contributes to CKD-induced enlargement of infarct size. CKD was induced in rats by 5/6 nephrectomy (SNx group) 4 weeks before myocardial infarction experiments, and sham-operated rats served as controls (Sham group). Infarct size as a percentage of area at risk after ischemia/reperfusion was significantly larger in the SNx group than in the Sham group (56...
May 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28404797/self-adjuvanting-c18-lipid-vinil-sulfone-pp2a-vaccine-study-of-the-induced-immunomodulation-against-trichuris-muris-infection
#8
M Gomez-Samblas, J J García-Rodríguez, M Trelis, D Bernal, F J Lopez-Jaramillo, F Santoyo-Gonzalez, S Vilchez, A M Espino, F Bolás-Fernández, A Osuna
Despite the importance of the adjuvant in the immunization process, very few adjuvants merge with the antigens in vaccines. A synthetic self-adjuvant oleic-vinyl sulfone (OVS) linked to the catalytic region of recombinant serine/threonine phosphatase 2A from the nematode Angiostrongylus costaricensis (rPP2A) was used for intranasal immunization in mice previously infected with Trichuris muris The animal intranasal immunization with rPP2A-OVS showed a reduction of 99.01% in the number of the nematode eggs and 97...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28404789/the-pp2a-b56-phosphatase-promotes-the-association-of-cdc20-with-apc-c-in-mitosis
#9
Sun Joo Lee, Veronica Rodriguez-Bravo, Hyunjung Kim, Sutirtha Datta, Emily A Foley
PP2A(B56) is a serine/threonine phosphatase essential for mitosis. At the kinetochore, PP2A(B56) both stabilizes microtubule binding and promotes silencing of the spindle assembly checkpoint (SAC) through its association with the SAC protein BubR1. Cells depleted of the B56 regulatory subunits of PP2A are delayed in APC/C(Cdc20) activation, an essential step for mitotic exit. It has been hypothesized that this delay arises from increased production of the mitotic checkpoint complex (MCC), an APC/C(Cdc20) inhibitor formed at unattached kinetochores through SAC signaling...
April 12, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28402338/insulin-deprivation-induces-pp2a-inhibition-and-tau-hyperphosphorylation-in-htau-mice-a-model-of-alzheimer-s-disease-like-tau-pathology
#10
Maud Gratuze, Jacinthe Julien, Franck R Petry, Françoise Morin, Emmanuel Planel
Abnormally hyperphosphorylated tau aggregated as intraneuronal neurofibrillary tangles is one of the two neuropathological hallmarks of Alzheimer's disease (AD). The majority of AD cases are sporadic with numerous environmental, biological and genetic risks factors. Interestingly, insulin dysfunction and hyperglycaemia are both risk factors for sporadic AD. However, how hyperglycaemia and insulin dysfunction affect tau pathology, is not well understood. In this study, we examined the effects of insulin deficiency on tau pathology in transgenic hTau mice by injecting different doses of streptozotocin (STZ), a toxin that destroys insulin-producing cells in the pancreas...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28402257/-dead-box-rna-helicase-3-modulates-nf-%C3%AE%C2%BAb-signal-pathway-by-controlling-the-phosphorylation-of-pp2a-c-subunit
#11
Xin Wang, Rui Wang, Miao Luo, Chen Li, Hua-Xia Wang, Chang-Chao Huan, Yu-Rong Qu, Ying Liao, Xiang Mao
Asp-Glu-Ala-Asp (DEAD)-box RNA helicase 3 (DDX3), an ATP-dependent RNA helicase, is associated with RNA splicing, mRNA export, transcription, translation, and RNA decay. Recent studies revealed that DDX3 participates in innate immune response during virus infection by interacting with TBK1 and regulating the production of IFN-β. In our studies, we demonstrated that DDX3 regulated NF-κB signal pathway. We found that DDX3 knockdown reduced the phosphorylation of p65 and IKK-β and ultimately attenuated the production of inflammatory cytokines induced by poly(I:C) or TNF-α stimulation...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28396515/light-involved-regulation-of-bzr1-stability-andphosphorylation-statusto-coordinate-plant-growth-in-arabidopsis
#12
Qian-Feng Li, Li-Chun Huang, Ke Wei, Jia-Wen Yu, Chang-Quan Zhang, Qiao-Quan Liu
Light and Brassinosteroid (BR) are master environmental stimulus and endogenous cue for plant growth and development, respectively. Great progress has been made in elucidating the molecular mechanisms on the crosstalk between light and BR. However, little is known about how BZR1, the pivotal integration node, is regulated by light and dark. Here, we demonstrated that an intact BR signaling pathway is essential for dark-induced hypocotyl elongation. Consequent expression assay showed that light-dark switch affected BZR1 phosphorylation and accumulation...
April 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28389570/bves-regulates-c-myc-stability-via-pp2a-and-suppresses-colitis-induced-tumourigenesis
#13
Bobak Parang, Andrew M Kaz, Caitlyn W Barrett, Sarah P Short, Wei Ning, Cody E Keating, Mukul K Mittal, Rishi D Naik, Mary K Washington, Frank L Revetta, J Joshua Smith, Xi Chen, Keith T Wilson, Thomas Brand, David M Bader, William P Tansey, Ru Chen, Teresa A Brentnall, William M Grady, Christopher S Williams
OBJECTIVE: Blood vessel epicardial substance (BVES) is a tight junction-associated protein that regulates epithelial-mesenchymal states and is underexpressed in epithelial malignancy. However, the functional impact of BVES loss on tumourigenesis is unknown. Here we define the in vivo role of BVES in colitis-associated cancer (CAC), its cellular function and its relevance to patients with IBD. DESIGN: We determined BVES promoter methylation status using an Infinium HumanMethylation450 array screen of patients with UC with and without CAC...
May 2017: Gut
https://www.readbyqxmd.com/read/28384260/denv-up-regulates-the-hmg-coa-reductase-activity-through-the-impairment-of-ampk-phosphorylation-a-potential-antiviral-target
#14
Rubén Soto-Acosta, Patricia Bautista-Carbajal, Margot Cervantes-Salazar, Antonio H Angel-Ambrocio, Rosa M Del Angel
Dengue is the most common mosquito-borne viral disease in humans. Changes of lipid-related metabolites in endoplasmic reticulum of dengue virus (DENV) infected cells have been associated with replicative complexes formation. Previously, we reported that DENV infection inhibits HMGCR phosphorylation generating a cholesterol-enriched cellular environment in order to favor viral replication. In this work, using enzymatic assays, ELISA, and WB we found a significant higher activity of HMGCR in DENV infected cells, associated with the inactivation of AMPK...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28382174/cysteine-transporter-slc3a1-promotes-breast-cancer-tumorigenesis
#15
Yang Jiang, Yuan Cao, Yongbin Wang, Wei Li, Xinyi Liu, Yixuan Lv, Xiaoling Li, Jun Mi
Cysteine is an essential amino acid for infants, aged people as well as patients with metabolic disorders. Although the thiol group of cysteine side chain is active in oxidative reactions, the role of cysteine in cancer remains largely unknown. Here, we report that the expression level of the solute carrier family 3, member 1 (SLC3A1), the cysteine carrier, tightly correlated with clinical stages and patients' survival. Elevated SLC3A1 expression accelerated the cysteine uptake and the accumulation of reductive glutathione (GSH), leading to reduced reactive oxygen species (ROS)...
2017: Theranostics
https://www.readbyqxmd.com/read/28381458/protein-phosphatase-2c-pp2c-is-responsible-for-vp-induced-dephosphorylation-of-aqp2-serine-261
#16
Pui W Cheung, Lars Ueberdiek, Jack Day, Richard Bouley, Dennis Brown
AQP2 trafficking is regulated by phosphorylation and dephosphorylation of serine residues in the AQP2 c-terminus. Vasopressin (VP) binding to its receptor (V2R) leads to a cascade of events that result in the phosphorylation of serine 256 (S256), S264 and S269, but dephosphorylation of S261. To identify which phosphatase is responsible for VP-induced S261 dephosphorylation, we pretreated cells with different phosphatase inhibitors before VP stimulation. Only sanguinarine, a specific protein phosphatase 2C (PP2C) inhibitor, abolished VP-induced S261 dephosphorylation, but not inhibitors of PP1, PP2A (okadaic acid) or PP2B (cyclosporine)...
April 5, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28374748/fasting-induced-hormonal-regulation-of-lysosomal-function
#17
Liqun Chen, Ke Wang, Aijun Long, Liangjie Jia, Yuanyuan Zhang, Haiteng Deng, Yu Li, Jinbo Han, Yiguo Wang
Lysosomes are centers for nutrient sensing and recycling that allow mammals to adapt to starvation. Regulation of lysosome dynamics by internal nutrient signaling is well described, but the mechanisms by which external cues modulate lysosomal function are unclear. Here, we describe an essential role of the fasting-induced hormone fibroblast growth factor 21 (FGF21) in lysosome homeostasis in mice. Fgf21 deficiency impairs hepatic lysosomal function by blocking transcription factor EB (TFEB), a master regulator of lysosome biogenesis and autophagy...
April 4, 2017: Cell Research
https://www.readbyqxmd.com/read/28370936/a-cascade-of-redox-reactions-generates-complexity-in-the-biosynthesis-of-the-protein-phosphatase-2-inhibitor-rubratoxin%C3%A2-a
#18
Jian Bai, Daojiang Yan, Tao Zhang, Yongzhi Guo, Yunbao Liu, Yi Zou, Mancheng Tang, Bingyu Liu, Qiong Wu, Shishan Yu, Yi Tang, Youcai Hu
Redox modifications are key complexity-generating steps in the biosynthesis of natural products. The unique structure of rubratoxin A (1), many of which arise through redox modifications, make it a nanomolar inhibitor of protein phosphatase 2A (PP2A). We identified the biosynthetic pathway of 1 and completely mapped the enzymatic sequence of redox reactions starting from the nonadride 5. Six redox enzymes are involved, including four α-ketoglutarate- and iron(II)-dependent dioxygenases that hydroxylate four sp(3) carbons; one flavin-dependent dehydrogenase that is involved in formation of the unsaturated lactone; and the ferric-reductase-like enzyme RbtH, which regioselectively reduces one of the maleic anhydride moieties in rubratoxin B to the γ-hydroxybutenolide that is critical for PP2A inhibition...
March 28, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28368396/activation-of-ck1%C3%A9-by-pp2a-pr61%C3%A9-is-required-for-the-initiation-of-wnt-signaling
#19
M Vinyoles, B Del Valle-Pérez, J Curto, M Padilla, A Villarroel, J Yang, A G de Herreros, M Duñach
No abstract text is available yet for this article.
April 3, 2017: Oncogene
https://www.readbyqxmd.com/read/28366644/a-metabolic-function-for-phospholipid-and-histone-methylation
#20
Cunqi Ye, Benjamin M Sutter, Yun Wang, Zheng Kuang, Benjamin P Tu
S-adenosylmethionine (SAM) is the methyl donor for biological methylation modifications that regulate protein and nucleic acid functions. Here, we show that methylation of a phospholipid, phosphatidylethanolamine (PE), is a major consumer of SAM. The induction of phospholipid biosynthetic genes is accompanied by induction of the enzyme that hydrolyzes S-adenosylhomocysteine (SAH), a product and inhibitor of methyltransferases. Beyond its function for the synthesis of phosphatidylcholine (PC), the methylation of PE facilitates the turnover of SAM for the synthesis of cysteine and glutathione through transsulfuration...
April 20, 2017: Molecular Cell
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