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https://www.readbyqxmd.com/read/29932870/er%C3%AE-36-gene-silencing-promotes-tau-protein-phosphorylation-inhibits-cell-proliferation-and-induces-apoptosis-in-human-neuroblastoma-sh-sy5y-cells
#1
Hong-Bin Wang, Tao Li, Dong-Zhou Ma, Hua Zhi
Neuroblastoma is the most common cancer in infants and the third most common cancer in children after leukemia and brain cancer. The purpose of our study was to investigate the effects of estrogen receptor (ER)-α36 gene silencing on tau protein phosphorylation, cell proliferation, and cell apoptosis in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with estrogen or left untreated, to investigate the effects of estrogen stimulation on ERα36 and the ERK/protein B kinase (AKT) signaling pathway...
June 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29884836/dephosphorylation-of-the-hiv-1-restriction-factor-samhd1-is-mediated-by-pp2a-b55%C3%AE-holoenzymes-during-mitotic-exit
#2
Kerstin Schott, Nina V Fuchs, Rita Derua, Bijan Mahboubi, Esther Schnellbächer, Janna Seifried, Christiane Tondera, Heike Schmitz, Caitlin Shepard, Alberto Brandariz-Nuñez, Felipe Diaz-Griffero, Andreas Reuter, Baek Kim, Veerle Janssens, Renate König
SAMHD1 is a critical restriction factor for HIV-1 in non-cycling cells and its antiviral activity is regulated by T592 phosphorylation. Here, we show that SAMHD1 dephosphorylation at T592 is controlled during the cell cycle, occurring during M/G1 transition in proliferating cells. Using several complementary proteomics and biochemical approaches, we identify the phosphatase PP2A-B55α responsible for rendering SAMHD1 antivirally active. SAMHD1 is specifically targeted by PP2A-B55α holoenzymes during mitotic exit, in line with observations that PP2A-B55α is a key mitotic exit phosphatase in mammalian cells...
June 8, 2018: Nature Communications
https://www.readbyqxmd.com/read/29848659/sphingolipids-inhibit-endosomal-recycling-of-nutrient-transporters-by-inactivating-arf6
#3
Brendan T Finicle, Manuel U Ramirez, Gang Liu, Elizabeth M Selwan, Alison N McCracken, Jingwen Yu, Yoosun Joo, Jannett Nguyen, Kevin Ou, Saurabh Ghosh Roy, Victor D Mendoza, Dania Virginia Corrales, Aimee L Edinger
Endogenous sphingolipids (ceramide) and related synthetic molecules (FTY720, SH-BC-893) reduce nutrient access by decreasing cell surface expression of a subset of nutrient transporter proteins. Here, we report that these sphingolipids disrupt endocytic recycling by inactivating the small GTPase ARF6. Consistent with reported roles for ARF6 in maintaining the tubular recycling endosome, MICAL-L1-positive tubules were lost from sphingolipid-treated cells. ARF6 inactivation may occur downstream of PP2A activation...
May 30, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29844427/pharmacologic-inhibition-of-protein-phosphatase-2a-achieves-durable-immune-mediated-antitumor-activity-when-combined-with-pd-1-blockade
#4
Winson S Ho, Herui Wang, Dominic Maggio, John S Kovach, Qi Zhang, Qi Song, Francesco M Marincola, John D Heiss, Mark R Gilbert, Rongze Lu, Zhengping Zhuang
Mounting evidence suggests that inhibition of protein phosphatase-2A (PP2A), a serine/threonine phosphatase, could enhance anticancer immunity. However, drugs targeting PP2A are not currently available. Here, we report that a PP2A inhibitor, LB-100, when combined with anti-PD-1 (aPD-1) blockade can synergistically elicit a durable immune-mediated antitumor response in a murine CT26 colon cancer model. This effect is T-cell dependent, leading to regression of a significant proportion of tumors. Analysis of tumor lymphocytes demonstrates enhanced effector T-cell and reduced suppressive regulatory T-cell infiltration...
May 29, 2018: Nature Communications
https://www.readbyqxmd.com/read/29743597/mastl-overexpression-promotes-chromosome-instability-and-metastasis-in-breast-cancer
#5
Samuel Rogers, Rachael A McCloy, Benjamin L Parker, David Gallego-Ortega, Andrew M K Law, Venessa T Chin, James R W Conway, Dirk Fey, Ewan K A Millar, Sandra O'Toole, Niantao Deng, Alexander Swarbrick, Paul D Chastain, Anthony J Cesare, Paul Timpson, C Elizabeth Caldon, David R Croucher, David E James, D Neil Watkins, Andrew Burgess
MASTL kinase is essential for correct progression through mitosis, with loss of MASTL causing chromosome segregation errors, mitotic collapse and failure of cytokinesis. However, in cancer MASTL is most commonly amplified and overexpressed. This correlates with increased chromosome instability in breast cancer and poor patient survival in breast, ovarian and lung cancer. Global phosphoproteomic analysis of immortalised breast MCF10A cells engineered to overexpressed MASTL revealed disruption to desmosomes, actin cytoskeleton, PI3K/AKT/mTOR and p38 stress kinase signalling pathways...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29568966/ppp2r2d-a-regulatory-subunit-of-protein-phosphatase-2a-promotes-gastric-cancer-growth-and-metastasis-via-mechanistic-target-of-rapamycin-activation
#6
Shijun Yu, Li Li, Qiong Wu, Ning Dou, Yandong Li, Yong Gao
Protein phosphatase 2A (PP2A) is an essential serine/threonine protein phosphatase that regulates the basic activities of eukaryotes by dephosphorylating its substrates. The function and substrate specificity of PP2A are generally determined by its regulatory subunits. In the present study, the clinical significance and roles of PPP2R2D, one of the regulatory subunits of PP2A, were demonstrated in gastric cancer (GC) carcinogenesis. Through a tissue microarray and quantitative polymerase chain reaction analysis, it was demonstrated that PPP2R2D was commonly upregulated in GC samples...
June 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29321323/hiv-1-vif-s-capacity-to-manipulate-the-cell-cycle-is-species-specific
#7
Edward L Evans, Jordan T Becker, Stephanie L Fricke, Kishan Patel, Nathan M Sherer
Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production, reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors cyclin T1 (CCNT1) and exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's postintegration stages, we studied HIV-1NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1-compatible versions of CCNT1 and XPO1 (3T3...
April 1, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29299971/the-role-of-the-fas-fasl-signaling-pathway-in-environmental-toxicant-induced-testicular-cell-apoptosis-an-update
#8
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...
April 2018: Systems Biology in Reproductive Medicine
https://www.readbyqxmd.com/read/29203851/dynamic-landscape-of-the-local-translation-at-activated-synapses
#9
T M Khlebodarova, V V Kogai, E A Trifonova, V A Likhoshvai
The mammalian target of rapamycin (mTOR) signaling pathway is the central regulator of cap-dependent translation at the synapse. Disturbances in mTOR pathway have been associated with several neurological diseases, such as autism and epilepsy. RNA-binding protein FMRP, a negative regulator of translation initiation, is one of the key components of the local translation system. Activation and inactivation of FMRP occurs via phosphorylation by S6 kinase and dephosphorylation by PP2A phosphatase, respectively...
January 2018: Molecular Psychiatry
https://www.readbyqxmd.com/read/29056830/aloperine-protects-mice-against-dss-induced-colitis-by-pp2a-mediated-pi3k-akt-mtor-signaling-suppression
#10
Xiaoxia Fu, Fei Sun, Faxi Wang, Junai Zhang, Biying Zheng, Jixin Zhong, Tiantian Yue, Xuebao Zheng, Jun-Fa Xu, Cong-Yi Wang
Colitis is a major form of inflammatory bowel disease which involved mucosal immune dysfunction. Aloperine is an alkaloid isolated from the shrub Sophora alopecuroides L. and has been recognized as an effective treatment for inflammatory and allergic diseases. The present study aimed to examine the molecular mechanisms underlying aloperine-mediated colitis protection. We found that aloperine treatment improved colitis induced by dextran sodium sulfate (DSS) based on body weight, disease activity index, colonic length, and spleen index...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/29028833/merkel-cell-polyomavirus-recruits-mycl-to-the-ep400-complex-to-promote-oncogenesis
#11
Jingwei Cheng, Donglim Esther Park, Christian Berrios, Elizabeth A White, Reety Arora, Rosa Yoon, Timothy Branigan, Tengfei Xiao, Thomas Westerling, Alexander Federation, Rhamy Zeid, Benjamin Strober, Selene K Swanson, Laurence Florens, James E Bradner, Myles Brown, Peter M Howley, Megha Padi, Michael P Washburn, James A DeCaprio
Merkel cell carcinoma (MCC) frequently contains integrated copies of Merkel cell polyomavirus DNA that express a truncated form of Large T antigen (LT) and an intact Small T antigen (ST). While LT binds RB and inactivates its tumor suppressor function, it is less clear how ST contributes to MCC tumorigenesis. Here we show that ST binds specifically to the MYC homolog MYCL (L-MYC) and recruits it to the 15-component EP400 histone acetyltransferase and chromatin remodeling complex. We performed a large-scale immunoprecipitation for ST and identified co-precipitating proteins by mass spectrometry...
October 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28884018/pp2a-b-holoenzyme-substrate-recognition-regulation-and-role-in-cytokinesis
#12
Cheng-Guo Wu, Hui Chen, Feng Guo, Vikash K Yadav, Sean J Mcilwain, Michael Rowse, Alka Choudhary, Ziqing Lin, Yitong Li, Tingjia Gu, Aiping Zheng, Qingge Xu, Woojong Lee, Eduard Resch, Benjamin Johnson, Jenny Day, Ying Ge, Irene M Ong, Mark E Burkard, Ylva Ivarsson, Yongna Xing
Protein phosphatase 2A (PP2A) is a major Ser/Thr phosphatase; it forms diverse heterotrimeric holoenzymes that counteract kinase actions. Using a peptidome that tiles the disordered regions of the human proteome, we identified proteins containing [LMFI]xx[ILV]xEx motifs that serve as interaction sites for B'-family PP2A regulatory subunits and holoenzymes. The B'-binding motifs have important roles in substrate recognition and in competitive inhibition of substrate binding. With more than 100 novel ligands identified, we confirmed that the recently identified LxxIxEx B'α-binding motifs serve as common binding sites for B' subunits with minor variations, and that S/T phosphorylation or D/E residues at positions 2, 7, 8 and 9 of the motifs reinforce interactions...
2017: Cell Discovery
https://www.readbyqxmd.com/read/28770955/the-regulatory-role-of-dopamine-receptor-d1-on-pp2a-via-sumo-1-modification
#13
C-Q Yu, L-Q Yin, Z-T Tu, D-W Liu, W-P Luo
OBJECTIVE: Renal dopamine receptor D1 played a critical role in the regulation of body blood pressure. Under hypertension, over-phosphorylation of D1 receptor impaired its function. G protein kinase 4 (GRK4) and protein phosphatase 2A (PP2A) exerted the effect to phosphorylate and de-phosphorylate D1 receptor. A current study revealed that the inhibition of GRK4 cannot normalize the phosphorylation level of D1 receptor. Meanwhile, the PP2A was activated under hypertension, indicating abnormal de-phosphorylation function of D1 receptor, the reason for which remains unknown...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28760745/a-pp2a-mediated-feedback-mechanism-controls-ca-2-dependent-no-synthesis-under-physiological-oxygen
#14
Thomas P Keeley, Richard C M Siow, Ron Jacob, Giovanni E Mann
Intracellular O2 is a key regulator of NO signaling, yet most in vitro studies are conducted in atmospheric O2 levels, hyperoxic with respect to the physiologic milieu. We investigated NO signaling in endothelial cells cultured in physiologic (5%) O2 and stimulated with histamine or shear stress. Culture of cells in 5% O2 (>5 d) decreased histamine- but not shear stress-stimulated endothelial (e)NOS activity. Unlike cells adapted to a hypoxic environment (1% O2 ), those cultured in 5% O2 still mobilized sufficient Ca2+ to activate AMPK...
December 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28736280/the-serine-threonine-protein-phosphatase-2a-controls-autoimmunity
#15
Amir Sharabi, Isaac R Kasper, George C Tsokos
Protein phosphatase 2A (PP2A) is the first serine/threonine phosphatase recognized to contribute to human and murine lupus immunopathology. PP2A expression in SLE is controlled both epigenetically and genetically, and it is increased in patients with SLE, which contributes to decreased IL-2 production, decreased CD3ζ and increased FcRγ expression on the surface of T cells, increased CREMα expression, hypomethylation of genes associated with SLE pathogenesis, and increased IL-17 production. β regulatory subunit of PP2A regulates IL-2 deprivation-induced T cell death and is decreased in SLE patients...
January 2018: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28678890/platinum-sensitive-2-like-impacts-growth-root-morphology-seed-set-and-stress-responses
#16
Amr R A Kataya, Maria T Creighton, Toga P Napitupulu, Christine Sætre, Behzad Heidari, Peter Ruoff, Cathrine Lillo
Eukaryotic protein phosphatase 4 (PP4) is a PP2A-type protein phosphatase that is part of a conserved complex with regulatory factors PSY2 and PP4R2. Various lines of Arabidopsis thaliana with mutated PP4 subunit genes were constructed to study the so far completely unknown functions of PP4 in plants. Mutants with knocked out putative functional homolog of the PSY2 LIKE (PSY2L) gene were dwarf and bushy, while plants with knocked out PP4R2 LIKE (PP4R2L) looked very similar to WT. The psy2l seedlings had short roots with disorganized morphology and impaired meristem...
2017: PloS One
https://www.readbyqxmd.com/read/28655554/t-type-ca-2-channels-elicit-pro-proliferative-and-anti-apoptotic-responses-through-impaired-pp2a-akt1-signaling-in-pasmcs-from-patients-with-pulmonary-arterial-hypertension
#17
Safietou Sankhe, Sevasti Manousakidi, Fabrice Antigny, Jennifer Arthur Ataam, Sana Bentebbal, Yann Ruchon, Florence Lecerf, Jessica Sabourin, Laura Price, Elie Fadel, Peter Dorfmüller, Saadia Eddahibi, Marc Humbert, Frédéric Perros, Véronique Capuano
Idiopathic pulmonary arterial hypertension (iPAH) is characterized by obstructive hyperproliferation and apoptosis resistance of distal pulmonary artery smooth muscle cells (PASMCs). T-type Ca2+ channel blockers have been shown to reduce experimental pulmonary hypertension, although the impact of T-type channel inhibition remains unexplored in PASMCs from iPAH patients. Here we show that T-type channels Cav3.1 and Cav3.2 are present in the lung and PASMCs from iPAH patients and control subjects. The blockade of T-type channels by the specific blocker, TTA-A2, prevents cell cycle progression and PASMCs growth...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28612433/musculin-inhibits-human-t-helper-17-cell-response-to-interleukin-2-by-controlling-stat5b-activity
#18
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 upregulation of PPP2R2B, a regulatory member of the protein phosphatase 2A (PP2A) enzyme...
September 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28512245/merkel-cell-polyomavirus-small-t-antigen-initiates-merkel-cell-carcinoma-like-tumor-development-in-mice
#19
Monique E Verhaegen, Doris Mangelberger, Paul W Harms, Markus Eberl, Dawn M Wilbert, Julia Meireles, Christopher K Bichakjian, Thomas L Saunders, Sunny Y Wong, Andrzej A Dlugosz
Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC...
June 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28500640/dysregulation-of-the-mek-erk-mnk1-signalling-cascade-by-middle-t-antigen-of-the-trichoydsplasia-spinulosa-polyomavirus
#20
J H Wu, D Narayanan, R A Simonette, P L Rady, S K Tyring
BACKGROUND: Trichodysplasia spinulosa (TS) is a disfiguring folliculocentric cutaneous disease caused by infection with the trichodysplasia spinulosa polyomavirus (TSPyV). The TSPyV genome contains splice variants encoding the middle tumour (mT) antigen, although the potential role for TSPyV mT antigen in disease development remains unknown. OBJECTIVE: The current study was designed to investigate the mechanistic properties of TSPyV mT antigen, which may further our understanding of TS pathogenesis and provide insight into potential therapies...
May 13, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
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