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https://www.readbyqxmd.com/read/28648781/pp2a-controls-genome-integrity-by-integrating-nutrient-sensing-and-metabolic-pathways-with-the-dna-damage-response
#1
Elisa Ferrari, Christopher Bruhn, Marta Peretti, Corinne Cassani, Walter Vincenzo Carotenuto, Mohamed Elgendy, Ghadeer Shubassi, Chiara Lucca, Rodrigo Bermejo, Mario Varasi, Saverio Minucci, Maria Pia Longhese, Marco Foiani
Mec1(ATR) mediates the DNA damage response (DDR), integrating chromosomal signals and mechanical stimuli. We show that the PP2A phosphatases, ceramide-activated enzymes, couple cell metabolism with the DDR. Using genomic screens, metabolic analysis, and genetic and pharmacological studies, we found that PP2A attenuates the DDR and that three metabolic circuits influence the DDR by modulating PP2A activity. Irc21, a putative cytochrome b5 reductase that promotes the condensation reaction generating dihydroceramides (DHCs), and Ppm1, a PP2A methyltransferase, counteract the DDR by activating PP2A; conversely, the nutrient-sensing TORC1-Tap42 axis sustains DDR activation by inhibiting PP2A...
June 12, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28643116/express-yourself-how-pp2a-b55-pab1-helps-torc1-talk-to-torc2
#2
REVIEW
Ruth Martín, Sandra Lopez-Aviles
The control of cell fate, growth and proliferation in response to nitrogen availability is a tightly controlled process, with the two TOR complexes (TORC1 and TORC2) and their effectors playing a central role. PP2A-B55(Pab1) has recently been shown to be a key element in this response in fission yeast, where it regulates cell cycle progression and sexual differentiation. Importantly, a recent study from our group has shown that PP2A-B55(Pab1) acts as a mediator between the activities of the two TOR signaling modules, enabling a crosstalk that is required to engage in the differentiation program...
June 22, 2017: Current Genetics
https://www.readbyqxmd.com/read/28641077/inhibition-of-early-growth-response-1-in-the-hippocampus-alleviates-neuropathology-and-improves-cognition-in-an-alzheimer-model-with-plaques-and-tangles
#3
Xike Qin, Yunling Wang, Hemant K Paudel
A sporadic form of Alzheimer disease (AD) and vascular dementia share many risk factors, and their pathogenic mechanisms are suggested to be related. Transcription factor early growth response 1 (Egr-1) regulates various vascular pathologies and is up-regulated in both AD brains and AD mouse models; however, its role in AD pathogenesis is unclear. Herein, we report that silencing of Egr-1 in the hippocampus by shRNA reduces tau phosphorylation, amyloid-β (Aβ) pathology, and improves cognition in the 3xTg-AD mouse model...
June 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28635628/identification-and-validation-of-reference-genes-for-seashore-paspalum-response-to-abiotic-stresses
#4
Yu Liu, Jun Liu, Lei Xu, Hui Lai, Yu Chen, Zhimin Yang, Bingru Huang
Seashore paspalum (Paspalum vaginatum) is among the most salt- and cadmium-tolerant warm-season perennial grass species widely used as turf or forage. The objective of this study was to select stable reference genes for quantitative real-time polymerase chain reaction (qRT-PCR) analysis of seashore paspalum in response to four abiotic stresses. The stability of 12 potential reference genes was evaluated by four programs (geNorm, NormFinder, BestKeeper, and RefFinder). U2AF combined with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) showed stable expression in Cd-treated leaves and cold-treated roots...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28634862/effect-of-gapt-extract-on-expression-of-tau-protein-and-its-phosphorylation-related-enzymes-in-hippocampal-neurons-of-appv717i-transgenic-mice
#5
Jing-Nian Ni, Jing Shi, Xue-Kai Zhang, Yi-Chang Yang, Xiao-Meng Liu, Ming-Qing Wei, Ting Li, Peng-Wen Wang, Jin-Zhou Tian, Yong-Yan Wang
OBJECTIVE: To investigate the effect of GAPT, an extract mixture from Radix Ginseng, Rhizoma Acor tatarinowii, Radix Polygalae and Radix Curcuma (containing ingredient of turmeric), etc. on expression of tau protein and its phosphorylation related enzyme in hippocampal neurons of APPV717I transgenic mice. METHODS: Sixty three-month-old APPV717I transgenic mice were randomly divided into model group, donepezil group [0.92 mg/(kg d)], the low, medium and high dosage of GAPT groups [0...
June 20, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28619992/patterning-and-gastrulation-defects-caused-by-the-t-w18-lethal-are-due-to-loss-of-ppp2r1a
#6
Lisette Lange, Matthias Marks, Jinhua Liu, Lars Wittler, Hermann Bauer, Sandra Piehl, Gabriele Bläß, Bernd Timmermann, Bernhard G Herrmann
The mouse t haplotype, a variant 20 cM genomic region on Chromosome 17, harbors 16 embryonic control genes identified by recessive lethal mutations isolated from wild mouse populations. Due to technical constraints so far only one of these, the t(w5) lethal, has been cloned and molecularly characterized. Here we report the molecular isolation of the t(w18) lethal. Embryos carrying the t(w18) lethal die from major gastrulation defects commencing with primitive streak formation at E6.5. We have used transcriptome and marker gene analyses to describe the molecular etiology of the t(w18) phenotype...
June 15, 2017: Biology Open
https://www.readbyqxmd.com/read/28619847/targeted-activation-of-the-shp-1-pp2a-signalling-axis-elicits-apoptosis-of-chronic-lymphocytic-leukemia-cells
#7
Elena Tibaldi, Mario Angelo Pagano, Federica Frezzato, Valentina Trimarco, Monica Facco, Giuseppe Zagotto, Giovanni Ribaudo, Valeria Pavan, Luciana Bordin, Andrea Visentin, Francesca Zonta, Gianpietro Semenzato, Anna Maria Brunati, Livio Trentin
The Src Family Kinase (SFK) Lyn is a key factor in the dysregulation of survival and apoptotic pathways of malignant B cells in chronic lymphocytic leukemia. One of the effects of Lyn's action is the spatial and functional segregation of the tyrosine phosphatase SHP-1 into two pools, one beneath the plasma membrane in an active state promoting pro-survival signals, the other in the cytosol in an inhibited conformation and unable to counter the elevated level of cytosolic tyrosine phosphorylation. We herein show that SHP-1 activity can be elicited directly by nintedanib, an agent also known as a triple angiokinase inhibitor, circumventing the phospho-S591-dependent inhibition of the phosphatase, leading to the dephosphorylation of pro-apoptotic players such as procaspase-8 and the serine/threonine phosphatase 2A, eventually triggering apoptosis...
June 15, 2017: Haematologica
https://www.readbyqxmd.com/read/28613156/reciprocal-regulation-of-arpp-16-by-pka-and-mast-3-kinases-provides-a-camp-regulated-switch-in-protein-phosphatase-2a-inhibition
#8
Veronica Musante, Lu Li, Jean Kanyo, Tukiet T Lam, Christopher M Colangelo, Shuk Kei Cheng, Harrison Brody, Paul Greengard, Nicolas Le Novère, Angus C Nairn
ARPP-16, ARPP-19, and ENSA are inhibitors of protein phosphatase PP2A. ARPP-19 and ENSA phosphorylated by Greatwall kinase inhibit PP2A during mitosis. ARPP-16 is expressed in striatal neurons where basal phosphorylation by MAST3 kinase inhibits PP2A and regulates key components of striatal signaling. The ARPP-16/19 proteins were discovered as substrates for PKA, but the function of PKA phosphorylation is unknown. We find that phosphorylation by PKA or MAST3 mutually suppresses the ability of the other kinase to act on ARPP-16...
June 14, 2017: ELife
https://www.readbyqxmd.com/read/28612433/musculin-inhibits-human-t-helper-17-cell-response-to-interleukin-2-by-controlling-stat5b-activity
#9
Veronica Santarlasci, Alessio Mazzoni, Manuela Capone, Maria Caterina Rossi, Laura Maggi, Gianni Montaini, Beatrice Rossettini, Rolando Cimaz, Matteo Ramazzotti, Giusi Barra, Raffaele De Palma, Enrico Maggi, Francesco Liotta, Lorenzo Cosmi, Sergio Romagnani, Francesco Annunziato
We recently demonstrated that human T helper (Th) 17 cells, unlike Th1 cells, do not proliferate in response to T-cell receptor stimulation, mainly because of their reduced capacity to produce and respond to IL-2. In this study we show that their lower responsiveness to IL-2 is due to the selective expression of Musculin (MSC), a member of the basic helix-loop-helix transcription factors. We show that MSC expression in human Th17 cells is retinoic acid orphan receptor (ROR)γt-dependent, and allows the up-regulation of PPP2R2B, a regulatory member of the protein phosphatase 2A (PP2A) enzyme...
June 14, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28609714/mfhas1-suppresses-tlr4-signaling-pathway-via-induction-of-pp2a-c-subunit-cytoplasm-translocation-and-inhibition-of-c-jun-dephosphorylation-at-thr239
#10
Qiqing Shi, Bo Xiong, Jing Zhong, Huihui Wang, Duan Ma, Changhong Miao
TLR4, an important Toll-like receptor in innate immunity, can be activated by LPS and induce proinflammatory cytokines to resist invasion of pathogenic microorganism, but excessive inflammation can trigger tissue injury. Many genes negatively regulate TLR4 signaling pathway. Recent studies found that malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) suppressed the expression of cytokine IL6 in Raw264.7 cells stimulated by LPS, but the mechanisms remained unclear. This study investigated the role of MFHAS1 in TLR4 signaling pathway and the possible mechanisms implicated...
June 10, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28603063/overexpression-of-phosphoprotein-phosphatase-2a-predicts-worse-prognosis-in-patients-with-breast-cancer-a-15-year-follow-up
#11
Po-Ming Chen, Pei-Yi Chu, Shiao-Lin Tung, Chun-Yu Liu, Yi-Fang Tsai, Yen-Shu Lin, Wan-Lun Wang, Yu-Ling Wang, Pei-Ju Lien, Ta-Chung Chao, Ling-Ming Tseng
Breast cancer subtypes can be stratified by immunohistochemical (IHC) expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2). The signaling pathways mediated by these receptors are the dominant drivers of cell proliferation and survival in the majority of human breast cancers. One of the most frequently overactivated pathways in breast cancer is the AKT signaling cascade. Protein phosphatase 2A (PP2A) acts as a switch to turn off signal transduction in the AKT pathway; however, it is frequently inactivated in many cancers by phosphorylation of Tyr-307 to form phosphoprotein phosphatase 2A (p-PP2A)...
June 8, 2017: Human Pathology
https://www.readbyqxmd.com/read/28600888/homeostatic-control-of-start-through-negative-feedback-between-cln3-cdk1-and-rim15-greatwall-kinase-in-budding-yeast
#12
Nicolas Talarek, Elisabeth Gueydon, Etienne Schwob
How cells coordinate growth and division is key for size homeostasis. Phosphorylation by G1-CDK of Whi5/Rb inhibitors of SBF/E2F transcription factors triggers irreversible S-phase entry in yeast and metazoans, but why this occurs at a given cell size is not fully understood. We show that the yeast Rim15-Igo1,2 pathway, orthologous to Gwl-Arpp19/ENSA, is up-regulated in early G1 and helps promoting START by preventing PP2ACdc55 to dephosphorylate Whi5. RIM15 overexpression lowers cell size while IGO1,2 deletion delays START in cells with low CDK activity...
June 10, 2017: ELife
https://www.readbyqxmd.com/read/28588271/pp2a-inhibition-from-lb100-therapy-enhances-daunorubicin-cytotoxicity-in-secondary-acute-myeloid-leukemia-via-mir-181b-1-upregulation
#13
Chao Hu, Mengxia Yu, Yanling Ren, Kongfei Li, Dominic M Maggio, Chen Mei, Li Ye, Juying Wei, Jie Jin, Zhengping Zhuang, Hongyan Tong
Patients with secondary acute myeloid leukemia (sAML) arising from myelodysplastic syndromes have a poor prognosis marked by an increased resistance to chemotherapy. An urgent need exists for adjuvant treatments that can enhance or replace current therapeutic options. Here we show the potential of LB100, a small-molecule protein phosphatase 2 A (PP2A) inhibitor, as a monotherapy and chemosensitizing agent for sAML using an in-vitro and in-vivo approach. We demonstrate that LB100 decreases cell viability through caspase activation and G2/M cell-cycle arrest...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28587927/the-%C3%AE-4-subunit-of-the-voltage-gated-calcium-channel-cacnb4-regulates-the-rate-of-cell-proliferation-in-chinese-hamster-ovary-cells
#14
Mohamad Rima, Marwa Daghsni, Stephan De Waard, Nathalie Gaborit, Ziad Fajloun, Michel Ronjat, Yasuo Mori, Juan L Brusés, Michel De Waard
The β subunits of Voltage-Gated Calcium Channel (VGCC) are cytosolic proteins that interact with the VGCC pore -forming subunit and participate in the trafficking of the channel to the cell membrane and in ion influx regulation. β subunits also exert functions independently of their binding to VGCC by translocation to the cell nucleus including the control of gene expression. Mutations of the neuronal Cacnb4 (β4) subunit are linked to human neuropsychiatric disorders including epilepsy and intellectual disabilities...
June 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28586756/inhibitors-of-the-pi3k-mtor-pathway-prevent-stat5-phosphorylation-in-jak2v617f-mutated-cells-through-pp2a-cip2a-axis
#15
Niccolò Bartalucci, Laura Calabresi, Manjola Balliu, Serena Martinelli, Maria Caterina Rossi, Jean Luc Villeval, Francesco Annunziato, Paola Guglielmelli, Alessandro M Vannucchi
Inhibition of the constitutively activated JAK/STAT pathway in JAK2V617F mutated cells by the JAK1/JAK2 inhibitor ruxolitinib resulted in clinical benefits in patients with myeloproliferative neoplasms. However, evidence of disease-modifying effects remains scanty; furthermore, some patients do not respond adequately to ruxolitinib, or have transient responses, thus novel treatment strategies are needed. Here we demonstrate that ruxolitinib causes incomplete inhibition of STAT5 in JAK2V617F mutated cells due to persistence of phosphorylated serine residues of STAT5b, that conversely are targeted by PI3K and mTORC1 inhibitors...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28586109/fyn-kinase-mediates-cortical-actin-ring-depolymerization-required-for-mast-cell-migration-in-response-to-tgf-%C3%AE-in-mice
#16
Karla A Ramírez-Valadez, Genaro Vázquez-Victorio, Marina Macías-Silva, Claudia González-Espinosa
Transforming Growth Factor-β (TGF-β) is a potent mast cell (MC) chemoattractant able to modulate local inflammatory reactions. The molecular mechanism leading to TGF-β-directed MC migration is not fully described. Here we analyzed the role of the Src family protein kinase Fyn on the main TGF-β-induced cytoskeletal changes leading to MC migration. Utilizing bone marrow-derived mast cells (BMMCs) from WT and Fyn-deficient mice we found that BMMC migration to TGF-β was impaired in the absence of the kinase...
June 6, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28585125/role-of-microtubule-associated-protein-tau-phosphorylation-in-alzheimer-s-disease
#17
REVIEW
Rong-Hong Ma, Yao Zhang, Xiao-Yue Hong, Jun-Fei Zhang, Jian-Zhi Wang, Gong-Ping Liu
As a major microtubule-associated protein, tau plays an important role in promoting microtubule assembly and stabilizing microtubules. In Alzheimer's disease (AD) and other tauopathies, the abnormally hyperphosphorylated tau proteins are aggregated into paired helical filaments and accumulated in the neurons with the form of neurofibrillary tangles. An imbalanced regulation in protein kinases and protein phosphatases is the direct cause of tau hyperphosphorylation. Among various kinases and phosphatases, glycogen synthase kinase-3β (GSK-3β) and protein phosphatase 2A (PP2A) are the most implicated...
June 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28577190/17%C3%AE-estradiol-and-or-estrogen-receptor-alpha-blocks-isoproterenol-induced-calcium-accumulation-and-hypertrophy-via-gsk3%C3%AE-pp2a-nfat3-anp-pathway
#18
Peiying Pai, Bharath Kumar Velmurugan, Chia-Hua Kuo, Chung-Yi Yen, Tsung-Jung Ho, Yueh-Min Lin, Yu-Feng Chen, Chao-Hung Lai, Cecilia Hsuan Day, Chih-Yang Huang
The present study was aimed to investigate the protective effects of 17β-estradiol (E2) and estrogen receptor α (ERα) on isoproterenol (ISO)-treated H9c2 cardiomyoblast cells. In the present study, we treated H9c2 cells with ISO, a β-adrenergic receptor agonist, to induce myocardiac hypertrophy. Pre-administration of E2 or ERα (induced by doxycycline) and E2 plus ERα significantly prevented ISO-induced increase of cell size and cytosolic calcium accumulation, accompanied with increased mRNA of atrial natriuretic peptide and brain natriuretic peptide...
June 2, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28571594/dual-torcs-driven-and-b56-orchestrated-signaling-network-guides-eukaryotic-cell-migration
#19
Lou W Kim
Different types of eukaryotic cells may adopt seemingly distinct modes of directional cell migration. However, several core aspects are regarded common whether the movement is either ameoboidal or mesenchymal. The region of cells facing the attractive signal is often termed leading edge where lamellipodial structures dominates and the other end of the cell called rear end is often mediating cytoskeletal F-actin contraction involving Myosin-II. Dynamic remodeling of cell-to-matrix adhesion involving integrin is also evident in many types of migrating cells...
June 2, 2017: BMB Reports
https://www.readbyqxmd.com/read/28562161/pp2a-b56%C3%AE-is-required-for-an-efficient-spindle-assembly-checkpoint
#20
Prajakta Varadkar, Fatima Abbasi, Kazuyo Takeda, Jade J Dyson, Brent McCright
The Spindle Assembly Checkpoint (SAC) is part of a complex feedback system designed to ensure that cells do not proceed through mitosis unless all chromosomal kinetochores have attached to spindle microtubules. The formation of the kinetochore complex and the implementation of the SAC are regulated by multiple kinases and phosphatases. BubR1 is a phosphoprotein that is part of the Cdc20 containing mitotic checkpoint complex that inhibits the APC/C so that Cyclin B1 and Securin are not degraded, thus preventing cells going into anaphase...
May 31, 2017: Cell Cycle
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