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Protein phosphatase 2a

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https://www.readbyqxmd.com/read/27913678/regulation-of-protein-phosphatase-2a-pp2a-tumor-suppressor-function-by-pme-1
#1
REVIEW
Amanpreet Kaur, Jukka Westermarck
Protein phosphatase 2A (PP2A) plays a major role in maintaining cellular signaling homeostasis by dephosphorylation of a variety of signaling proteins and acts as a tumor suppressor. Protein phosphatase methylesterase-1 (PME-1) negatively regulates PP2A activity by highly complex mechanisms that are reviewed here. Importantly, recent studies have shown that PME-1 promotes oncogenic MAPK/ERK and AKT pathway activities in various cancer types. In human glioma, high PME-1 expression correlates with tumor progression and kinase inhibitor resistance...
December 15, 2016: Biochemical Society Transactions
https://www.readbyqxmd.com/read/27901482/hyperglycemia-triggers-hipk2-protein-degradation
#2
Silvia Baldari, Alessia Garufi, Marisa Granato, Laura Cuomo, Giuseppa Pistritto, Mara Cirone, Gabriella D'Orazi
Homeodomain interacting protein kinase-2 (HIPK2) is an evolutionary conserved kinase that modulates several key molecular pathways to restrain tumor growth and induce p53-depending apoptotic cell-death in response to anticancer therapies. HIPK2 silencing in cancer cells leads to chemoresistance and cancer progression, in part due to p53 inhibition. Recently, hyperglycemia has been shown to reduce p53 phosphorylation at serine 46 (Ser46), the target residue of HIPK2, thus impairing p53 apoptotic function. Here we asked whether hyperglycemia could, upstream of p53, target HIPK2...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27889601/microcystin-lr-induced-liver-injury-in-mice-and-in-primary-human-hepatocytes-is-caused-by-oncotic-necrosis
#3
Benjamin L Woolbright, C David Williams, Hongmin Ni, Sean Kumer, Timothy Schmitt, Bartholomew Kane, Hartmut Jaeschke
Microcystins are a group of toxins produced by freshwater cyanobacteria. Uptake of microcystin-leucine arginine (MC-LR) by organic anion transporting polypeptide 1B2 in hepatocytes results in inhibition of protein phosphatase 1A and 2A, and subsequent cell death. Studies performed in primary rat hepatocytes demonstrate prototypical apoptosis after MC-LR exposure; however, no study has directly tested whether apoptosis is critically involved in vivo in the mouse, or in human hepatocytes. MC-LR (120 μg/kg) was administered to C57BL/6J mice and cell death was evaluated by alanine aminotransferase (ALT) release, caspase-3 activity in the liver, and histology...
November 23, 2016: Toxicon: Official Journal of the International Society on Toxinology
https://www.readbyqxmd.com/read/27886582/crude-extract-of-cyanobacteria-radiocystis-fernandoi-strain-r28-induces-liver-impairments-in-fish
#4
M G Paulino, D Tavares, F Bieczynski, P G Pedrão, N E S Souza, M M Sakuragui, C M Luquet, A P Terezan, J B Fernandes, A Giani, M N Fernandes
Radiocystis fernandoi R28 strain is a cyanobacterium which produces mostly the RR and YR microcystin variants (MC-RR and MC-YR, respectively). The effects of crude extract of the R. fernandoi strain R28 were evaluated on the protein phosphatases and on the structure and ultrastructure of the liver of the Neotropical fish, Hoplias malabaricus, after acute and subchronic exposure. Concomitantly, the accumulation of the majority of MCs was determined in the liver and muscle. The fish were exposed to 120.60 MC-RR+MC-LR kg-fish(-1) (=100μg MC-LReq kg-fish(-1)) for 12 and 96h (one single dose, acute exposure) and 30days (one similar dose every 72h, subchronic exposure)...
November 17, 2016: Aquatic Toxicology
https://www.readbyqxmd.com/read/27881117/novel-prokaryotic-expression-of-thioredoxin-fused-insulinoma-associated-protein-tyrosine-phosphatase-2-ia-2-its-characterization-and-immunodiagnostic-application
#5
Luciano Lucas Guerra, Natalia Inés Faccinetti, Aldana Trabucchi, Bruno David Rovitto, Adriana Victoria Sabljic, Edgardo Poskus, Ruben Francisco Iacono, Silvina Noemí Valdez
BACKGROUND: The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A)...
November 24, 2016: BMC Biotechnology
https://www.readbyqxmd.com/read/27872207/myeloid-specific-gene-deletion-of-protein-phosphatase-2a-magnifies-myd88-and-trif-dependent-inflammation-following-endotoxin-challenge
#6
Lei Sun, Tiffany T Pham, Timothy T Cornell, Kelli L McDonough, Walker M McHugh, Neal B Blatt, Mary K Dahmer, Thomas P Shanley
Protein phosphatase 2A (PP2A) is a member of the intracellular serine/threonine phosphatases. Innate immune cell activation triggered by pathogen-associated molecular patterns is mediated by various protein kinases, and PP2A plays a counter-regulatory role by deactivating these kinases. In this study, we generated a conditional knockout of the α isoform of the catalytic subunit of PP2A (PP2ACα). After crossing with myeloid-specific cre-expressing mice, effective gene knockout was achieved in various myeloid cells...
November 21, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27866533/-lb100-reverses-the-acquired-resistance-to-gefitinib-in-lung-adenocarcinoma-cells-with-egfr-mutation
#7
S Shan, Y D Wang, T Ren
Objective: To investigate the possibility of the Protein Phosphatase 2A (PP2A) inhibitor, LB100, in reversing acquired resistance to gefitinib in lung adenocarcinoma with epidermal growth factor receptor (EGFR) gene mutation. Methods: Cell line NCI-H1975 and established primary culture cell line 44-1 with gefitinib resistance were sequenced to determine the mutation type of EGFR gene. Cells were treated with gefitinib alone or combined with LB100 to determine the half maximal inhibitory concentration (IC50), and sensitivity of 44-1 and NCI-1975 to gefitinib alone or combined with LB100 was compared...
November 15, 2016: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/27855413/stimulation-of-suicidal-erythrocyte-death-by-phosphatase-inhibitor-calyculin-a
#8
Mustafa Almasry, Mohamed Jemaà, Morena Mischitelli, Caterina Faggio, Florian Lang
BACKGROUND/AIMS: The serine/threonine protein phosphatase 1 and 2a inhibitor Calyculin A may trigger suicidal death or apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include increase of cytosolic Ca2+ activity ([Ca2+] i). Eryptosis is fostered by activation of staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, and D4476 sensitive casein kinase...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27851811/atorvastatin-alleviates-experimental-diabetic-cardiomyopathy-by-regulating-the-gsk-3%C3%AE-pp2ac-nf-%C3%AE%C2%BAb-signaling-axis
#9
Xiao-Min Ren, Guang-Feng Zuo, Wen Wu, Jie Luo, Peng Ye, Shao-Liang Chen, Zuo-Ying Hu
Recent studies reported that atorvastatin (ATOR) alleviated progression of experimental diabetic cardiomyopathy (DCM), possibly by protecting against apoptosis. However, the underlying mechanisms of this protective effect remain unclear. Therefore, our study investigated the role of the glycogen synthase kinase (GSK)-3β-protein phosphatase 2A(PP2A)-NF-κB signaling pathway in the anti-apoptotic and cardioprotective effects of ATOR on cardiomyocytes cultured in high glucose (HG) and in DCM. Our results showed that, in HG-cultured cardiomyocytes, phosphorylation of GSK-3β was decreased, while that of the PP2A catalytic subunit C (PP2Ac) and IKK/IкBα was increased, followed by NF-кB nuclear translocation and apoptosis...
2016: PloS One
https://www.readbyqxmd.com/read/27849062/the-phosphorylated-form-of-fty720-activates-pp2a-represses-inflammation-and-is-devoid-of-s1p-agonism-in-a549-lung-epithelial-cells
#10
Md Mostafizur Rahman, Laura Prünte, Leonard F Lebender, Brijeshkumar S Patel, Ingrid Gelissen, Philip M Hansbro, Jonathan C Morris, Andrew R Clark, Nicole M Verrills, Alaina J Ammit
Protein phosphatase 2A (PP2A) activity can be enhanced pharmacologically by PP2A-activating drugs (PADs). The sphingosine analog FTY720 is the best known PAD and we have shown that FTY720 represses production of pro-inflammatory cytokines responsible for respiratory disease pathogenesis. Whether its phosphorylated form, FTY720-P, also enhances PP2A activity independently of the sphingosine 1-phosphate (S1P) pathway was unknown. Herein, we show that FTY720-P enhances TNF-induced PP2A phosphatase activity and significantly represses TNF-induced interleukin 6 (IL-6) and IL-8 mRNA expression and protein secretion from A549 lung epithelial cells...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27845735/deletion-of-pr130-interrupts-cardiac-development-in-zebrafish
#11
Jie Yang, Zuhua Li, Xuedong Gan, Gang Zhai, Jiajia Gao, Chenling Xiong, Xueping Qiu, Xuebin Wang, Zhan Yin, Fang Zheng
Protein phosphatase 2 regulatory subunit B, alpha (PPP2R3A), a regulatory subunit of protein phosphatase 2A (PP2A), is a major serine/threonine phosphatase that regulates crucial function in development and growth. Previous research has implied that PPP2R3A was involved in heart failure, and PR130, the largest transcription of PPP2R3A, functioning in the calcium release of sarcoplasmic reticulum (SR), plays an important role in the excitation-contraction (EC) coupling. To obtain a better understanding of PR130 functions in myocardium and cardiac development, two pr130-deletion zebrafish lines were generated using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated proteins (Cas) system...
November 11, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27836688/pathologic-significance-of-set-i2pp2a-mediated-pp2a-and-non-pp2a-pathways-in-polycystic-ovary-syndrome-pcos
#12
REVIEW
Shi-Wen Jiang, Siliang Xu, Haibin Chen, Xiaoqiang Liu, Zuoqing Tang, Yugui Cui, Jiayin Liu
SET (SE translocation, SET), a constitutive inhibitor of protein phosphatase 2A (PP2A), is a multifunctional oncoprotein involved in DNA replication, histone modification, nucleosome assembly, gene transcription and cell proliferation. It is widely expressed in human tissues including the gonadal system and brain. Intensive studies have shown that overexpressed SET plays an important role in the development of Alzheimer's disease (AD), and may also contribute to the malignant transformation of breast and ovarian cancers...
November 9, 2016: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/27832939/roles-and-regulation-of-protein-phosphatase-2a-pp2a-in-the-heart
#13
Ellen R Lubbers, Peter J Mohler
Reversible protein phosphorylation is central to a variety of cardiac processes including excitation-contraction coupling, Ca(2+) handling, cell metabolism, myofilament regulation, and cell-cell communication. While kinase pathways linked with elevated adrenergic signaling have been a major focus for the cardiovascular field over the past half century, new findings support the critical role of protein phosphatases in both health and disease. Protein phosphatase 2A (PP2A) is a central cardiac phosphatase that regulates diverse myocyte functions through a host of target molecules...
November 8, 2016: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/27812910/the-protein-phosphatase-2a-catalytic-subunit-stpp2ac2b-acts-as-a-positive-regulator-of-tuberization-induction-in-solanum-tuberosum-l
#14
María Noelia Muñiz García, María Catalina Muro, Luciana Carla Mazzocchi, Silvia Marina País, Margarita Stritzler, Mariana Schlesinger, Daniela Andrea Capiati
This study provides the first genetic evidence for the role of PP2A in tuberization, demonstrating that the catalytic subunit StPP2Ac2b positively modulates tuber induction, and that its function is related to the regulation of gibberellic acid metabolism. The results contribute to a better understanding of the molecular mechanism controlling tuberization induction, which remains largely unknown. The serine/threonine protein phosphatases type 2A (PP2A) are implicated in several physiological processes in plants, playing important roles in hormone responses...
November 3, 2016: Plant Molecular Biology
https://www.readbyqxmd.com/read/27799315/ep4-receptor-associated-protein-in-macrophages-protects-against-bleomycin-induced-pulmonary-inflammation-in-mice
#15
Sei Higuchi, Risako Fujikawa, Taichi Ikedo, Kosuke Hayashi, Mika Yasui, Manabu Nagata, Masato Nakatsuji, Masayuki Yokode, Manabu Minami
Excessive activation of inflammatory macrophages drives the pathogenesis of many chronic diseases. EP4 receptor-associated protein (EPRAP) has been identified as a novel, anti-inflammatory molecule in macrophages. In this study, we investigated the role of EPRAP using a murine model of bleomycin (BLM)-induced pulmonary inflammation. When compared with wild-type mice, EPRAP-deficient mice exhibited significantly higher mortality, and increased accumulation of macrophages and proinflammatory molecules in the lung 7 d post-BLM administration...
October 31, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27779687/gambogenic-acid-induces-proteasomal-degradation-of-cip2a-and-sensitizes-hepatocellular-carcinoma-to-anticancer-agents
#16
Xian-Jun Yu, Qun Zhao, Xuan-Bin Wang, Jing-Xuan Zhang, Xiao-Bo Wang
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein that is overexpressed in many human malignancies. It regulates phosphorylated AKT and stabilizes c‑Myc in cell proliferation and tumor formation, suggesting that CIP2A plays an essential role in the development of cancer. In the present study, we report that a natural compound, gambogenic acid (GEA), induced the degradation of CIP2A via the ubiquitin‑proteasome pathway. Interestingly, the combination of GEA and proteasome inhibitors potentiated the accumulation of ubiquitinated CIP2A and aggresome formation...
October 20, 2016: Oncology Reports
https://www.readbyqxmd.com/read/27775603/zinc-finger-and-x-linked-factor-zfx-binds-to-human-set-transcript-2-promoter-and-transactivates-set-expression
#17
Siliang Xu, Ping Duan, Jinping Li, Tristan Senkowski, Fengbiao Guo, Haibin Chen, Alberto Romero, Yugui Cui, Jiayin Liu, Shi-Wen Jiang
SET (SE Translocation) protein carries out multiple functions including those for protein phosphatase 2A (PP2A) inhibition, histone modification, DNA repair, and gene regulation. SET overexpression has been detected in brain neurons of patients suffering Alzheimer's disease, follicle theca cells of Polycystic Ovary Syndrome (PCOS) patients, and ovarian cancer cells, indicating that SET may play a pathological role for these disorders. SET transcript 2, produced by a specific promoter, represents a major transcript variant in different cell types...
October 20, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27774130/enhancing-therapeutic-efficacy-of-cisplatin-by-blocking-dna-damage-repair
#18
Yuwei Cong, Liangyan Wang, Zigui Wang, Shasha He, Dongfang Zhou, Xiabin Jing, Yubin Huang
Self-repair of nuclear DNA damage is the most known reason that leads to drug resistance of cancer tissue and limited therapeutic efficacy of anticancer drugs. Inhibition of protein phosphatase 2A (PP2A) would block DNA damage-induced defense of cancer cells to suppress DNA repair for enhanced cancer treatment. Here, we combined a PP2A inhibitor LB (4-(3-carboxy-7-oxa-bicyclo[2.2.1]heptane-2-carbonyl) piperazine-1-carboxylic acid tert-butyl ester) and the DNA damage chemotherapeutic drug cisplatin through a simple physical superposition...
October 13, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27759157/flexibility-vs-robustness-in-cell-cycle-regulation-of-timing-of-m-phase-entry-in-xenopus-laevis-embryo-cell-free-extract
#19
Mateusz Debowski, Mohammed El Dika, Jacek Malejczyk, Robert Zdanowski, Claude Prigent, Jean-Pierre Tassan, Malgorzata Kloc, Miroslaw Lachowicz, Jacek Z Kubiak
During the cell cycle, cyclin dependent kinase 1 (CDK1) and protein phosphatase 2A (PP2A) play major roles in the regulation of mitosis. CDK1 phosphorylates a series of substrates triggering M-phase entry. Most of these substrates are dephosphorylated by PP2A. To allow phosphorylation of CDK1 substrates, PP2A is progressively inactivated upon M-phase entry. We have shown previously that the interplay between these two activities determines the timing of M-phase entry. Slight diminution of CDK1 activity by the RO3306 inhibitor delays M-phase entry in a dose-dependent manner in Xenopus embryo cell-free extract, while reduction of PP2A activity by OA inhibitor accelerates this process also in a dose-dependent manner...
2016: International Journal of Developmental Biology
https://www.readbyqxmd.com/read/27758717/pharmacological-activation-of-protein-phosphatase-2-a-pp2a-activity-a-novel-strategy-to-fight-against-human-malignancies
#20
Maria Rosaria Carratù, Anna Signorile, Domenico De Rasmo, Antonia Reale, Angelo Vacca
BACKGROUND: The serine-threonine protein phosphatase 2A (PP2A) regulates multiple cell signaling cascades and its inactivation by viral oncoproteins, mutation of specific structural subunits or upregulation of the cellular endogenous inhibitors may contribute to malignant transformation by regulating specific phosphorylation events. Pharmacological modulation of PP2A activity is becoming an attractive strategy for cancer treatment. Some compounds targeting PP2A are able to induce PP2A reactivation and subsequent cell death in several types of cancer...
October 14, 2016: Current Medicinal Chemistry
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