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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/27889260/two-bistable-switches-govern-m-phase-entry
#3
Satoru Mochida, Scott Rata, Hirotsugu Hino, Takeharu Nagai, Béla Novák
The abrupt and irreversible transition from interphase to M phase is essential to separate DNA replication from chromosome segregation. This transition requires the switch-like phosphorylation of hundreds of proteins by the cyclin-dependent kinase 1 (Cdk1):cyclin B (CycB) complex. Previous studies have ascribed these switch-like phosphorylations to the auto-activation of Cdk1:CycB through the removal of inhibitory phosphorylations on Cdk1-Tyr15 [1, 2]. The positive feedback in Cdk1 activation creates a bistable switch that makes mitotic commitment irreversible [2-4]...
November 15, 2016: Current Biology: CB
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/27879191/replacement-of-sfc-dpi-with-sfc-mdi-exhaled-through-the-nose-improved-eosinophilic-chronic-rhinosinusitis-with-bronchial-asthma%C3%A2
#5
Yoshiki Kobayashi, Mikiya Asako, Takahisa Yamamoto, Hirotaka Yasuba, Koichi Tomoda, Akira Kanda
OBJECTIVE: Eosinophilic chronic rhinosinusitis (ECRS), a subgroup of chronic rhinosinusitis with nasal polyps, is a refractory disease closely associated with bronchial asthma. We recently reported on the efficacy of ultra-fine particle inhaled corticosteroids (ICS) (hydrofluoroalkane-134a-beclomethasone dipropionate: HFA-BDP) exhalation through the nose (ETN) treatment for mild-to-moderate asthmatics with ECRS. However, the effect of HFA-BDP ETN was found to be transient in some cases with severe ECRS and asthma, requiring treatment with higher-dose ICS and long-acting β2-agonists (LABA)...
November 23, 2016: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27872653/the-zuo-jin-wan-formula-induces-mitochondrial-apoptosis-of-cisplatin-resistant-gastric-cancer-cells-via-cofilin-1
#6
Qing-Feng Tang, Jian Sun, Hui Yu, Xiao-Jing Shi, Rong Lv, Hong-Chang Wei, Pei-Hao Yin
Despite the status of cisplatin (DDP) as a classical chemotherapeutic agent in the treatment of cancer, the development of multidrug resistance often leads to a failure of DDP therapy. Here we found that phosphorylated cofilin-1 (p-cofilin-1) was overexpressed in the DDP-resistant human gastric cancer cell lines SGC7901/DDP and BGC823/DDP, relative to the respective parent cell lines (SGC7901 and BGC823), and that DDP induced the dephosphorylation of p-cofilin-1 in both parent lines but not in the DDP-resistant lines...
2016: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/27872207/myeloid-specific-gene-deletion-of-protein-phosphatase-2a-magnifies-myd88-and-trif-dependent-inflammation-following-endotoxin-challenge
#7
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
#8
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/27865410/comparative-analysis-of-testis-transcriptomes-associated-with-male-infertility-in-cattleyak
#9
Xin Cai, Shumin Yu, TserangDonko Mipam, Fang Yang, Wangsheng Zhao, Wenjing Liu, SuiZhong Cao, Liuhong Shen, Fangfang Zhao, Lei Sun, Chuanfei Xu, Shixin Wu
Cattleyak exhibit equivalent adaptability to harsh environment as yak and much higher performances than yak. However, male infertility of cattleyak due to spermatogenic arrest greatly restricts their effective utilization in yak breeding. Although much work has been done to investigate the mechanisms of spermatogenic arrest, there is little information available in regard to the differences in transcriptomic profiling between cattleyak and yak testes. In this work, histologic observation indicated that spermatogonia were the main type of germ cells present in cattleyak testis, whereas all types of germ cells in differentiation were present in yak testis...
January 15, 2017: Theriogenology
https://www.readbyqxmd.com/read/27863840/long-term-pre-treatment-of-antioxidant-ginkgo-biloba-extract-egb-761-attenuates-cerebral-ischemia-induced-neuronal-damage-in-aged-mice
#10
Xiaomei Zhou, Yinliang Qi, Ting Chen
Antioxidant activity has been attributed to the neuroprotective effects of Ginkgo biloba extract EGb-761 on brain disorders including ischemic stroke. It is suggested that oxidative stress implicates in neuron injuries during aging. However, whether or not EGb-761 could be used to treat age-related cerebral ischemia is unclear. In the present study, we directly studied the protective effects of EGb-761 in brain ischemia in the mice with different age. As expected, the recovery from brain damages was impaired in aged mice (24 months) in an animal model of middle cerebral artery occlusion (MCAO)...
November 15, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27852846/a-transformation-defective-polyomavirus-middle-t-antigen-with-a-novel-defect-in-pi3-kinase-signaling
#11
Deborah Denis, Cecile Rouleau, Brian S Schaffhausen
: Middle T antigen (MT), the principal oncoprotein of murine polyomavirus, transforms by association with cellular proteins. PP2A, YAP, Src family tyrosine kinases, Shc, phosphoinositide-3-kinase (PI3K) and PLCγ1 have all been implicated in MT transformation. Mutant dl1015, deleting residues 338-347 in the C-terminal region, has been an enigma, because the basis for its transformation defect has not been apparent. This work probes the dl1015 region of MT. Because the region is proline rich, the hypothesis that it targets SH3 domains was tested, but mutation of the putative SH3 binding motif did not affect transformation...
November 16, 2016: Journal of Virology
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
#12
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
#13
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
#14
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
#15
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
#16
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/27827901/structure-activity-relationship-studies-using-natural-and-synthetic-okadaic-acid-dinophysistoxin-toxins
#17
Michael J Twiner, Gregory J Doucette, Yucheng Pang, Chao Fang, Craig J Forsyth, Christopher O Miles
Okadaic acid (OA) and the closely related dinophysistoxins (DTXs) are algal toxins that accumulate in shellfish and are known serine/threonine protein phosphatase (ser/thr PP) inhibitors. Phosphatases are important modulators of enzyme activity and cell signaling pathways. However, the interactions between the OA/DTX toxins and phosphatases are not fully understood. This study sought to identify phosphatase targets and characterize their structure-activity relationships (SAR) with these algal toxins using a combination of phosphatase activity and cytotoxicity assays...
November 4, 2016: Marine Drugs
https://www.readbyqxmd.com/read/27821484/protocadherin-7-acts-through-set-and-pp2a-to-potentiate-mapk-signaling-by-egfr-and-kras-during-lung-tumorigenesis
#18
Xiaorong Zhou, Barrett L Updegraff, Yabin Guo, Michael Peyton, Luc Girard, Jill E Larsen, Xian-Jin Xie, Yunyun Zhou, Tae Hyun Hwang, Yang Xie, Jaime Rodriguez-Canales, Pamela Villalobos, Carmen Behrens, Ignacio I Wistuba, John Minna, Kathryn A O'Donnell
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-associated deaths worldwide. Given the efficacy of membrane proteins as therapeutic targets in human malignancies, we examined cell-surface receptors that may act as drivers of lung tumorigenesis. Here we report that the PROTOCADHERIN PCDH7 is overexpressed frequently in NSCLC tumors where this event is associated with poor clinical outcome. PCDH7 overexpression synergized with EGFR and KRAS to induce MAPK signaling and tumorigenesis. Conversely, PCDH7 depletion suppressed ERK activation, sensitized cells to MEK inhibitors and reduced tumor growth...
November 7, 2016: Cancer Research
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
#19
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/27810903/nnmt-silencing-activates-tumor-suppressor-pp2a-inactivates-oncogenic-stks-and-inhibits-tumor-forming-ability
#20
Kamalakannan Palanichamy, Suman Kanji, Nicolaus Gordon, Krishnan Thirumoorthy, John R Jacob, Kevin T Litzenberg, Disha Patel, Arnab Chakravarti
PURPOSE: To identify potential molecular hubs that regulate oncogenic kinases and target them to improve treatment outcomes for glioblastoma (GBM) patients. EXPERIMENTAL DESIGN: Data mining of The Cancer Genome Atlas (TCGA) datasets identified Nicotinamide-N-methyl transferase (NNMT) as a prognostic marker for GBM, an enzyme linked to the reorganization of the methylome. We tested our hypothesis that NNMT plays a crucial role by modulating protein methylation leading to inactivation of tumor suppressors and activation of oncogenes...
November 3, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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