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Protein phosphatase 2a

Takanori Hayashi, Masahiro Hikichi, Jun Yukitake, Nobuhiro Harada, Toshiaki Utsumi
Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)α-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ERα serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ERα phosphorylation at Ser167...
December 2017: Oncology Letters
Jin Gao, Catherine M Cahill, Xudong Huang, Joshua L Roffman, Stefania Lamon-Fava, Maurizio Fava, David Mischoulon, Jack T Rogers
S-Adenosyl methionine (SAMe), as a major methyl donor, exerts its influence on central nervous system function through cellular transmethylation pathways, including the methylation of DNA, histones, protein phosphatase 2A, and several catecholamine moieties. Based on available evidence, this review focuses on the lifelong range of severe neuropsychiatric and neurodegenerative diseases and their associated neuropathologies, which have been linked to the deficiency/load of SAMe production or/and the disturbance in transmethylation pathways...
January 16, 2018: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Shuhei Enjoji, Ryotaro Yabe, Shunya Tsuji, Kazuhiro Yoshimura, Hideyoshi Kawasaki, Masashi Sakurai, Yusuke Sakai, Hiroko Takenouchi, Shigefumi Yoshino, Shoichi Hazama, Hiroaki Nagano, Hiroko Oshima, Masanobu Oshima, Michael P Vitek, Tetsuya Matsuura, Yoshitaka Hippo, Tatsuya Usui, Takashi Ohama, Koichi Sato
Gastric cancer is the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide. Chemotherapies against gastric cancer often fail, with cancer recurrence due potentially to the persistence of cancer stem cells. This unique subpopulation of cells in tumors possess the ability to self-renew and de-differentiate. These cancer stem cells are critical for initiation, maintenance, metastasis, and relapse of cancers; however, the molecular mechanisms supporting cancer stemness remain largely unknown...
January 12, 2018: Molecular Cancer Research: MCR
Jianhui Zhao, Zhongli Gao, Chao Zhang, Han Wu, Rui Gu, Rui Jiang
Osteosarcoma is the most common malignant bone tumor in children and adolescents with high rate of incidence, high frequency of recurrence and high degree of metastasis. This study aimed to investigate the effects of long noncoding RNA antisense ncRNA in the Abundant in neuroepithelium area (ANA)/B-cell translocation gene 3 (BTG3) locus (lncRNA ASBEL) on the pathogenesis of osteosarcoma. The expression levels of ASBEL in human osteoblast cells and human osteosarcoma cells were evaluated using qRT-PCR. Effects of ASBEL knockdown on cell viability, migration and invasion were detected using trypan blue exclusion assay, cell migration and invasion assay, respectively...
January 11, 2018: Journal of Cellular Biochemistry
Yuan Zhou, Xiao Geng, Yu Chen, Hao Shi, Yan Yang, Chan Zhu, Guang Yu, Zongxiang Tang
Microcystin (MC)-LR is a cyclic heptapeptide that acts as a potent reproductive system toxin. However, the underlying pathways of MCLR-induced reproductive system toxicity have not been well elucidated. The blood-testis barrier is mainly constituted by tight junctions (TJs) between adjacent Sertoli cells in the seminiferous epithelium near the basement membrane. The present study was designed to investigate changes in TJs and the underlying pathway in MC-LR-induced TJs toxicity in Sertoli cell. In our study, the transepithelial electrical resistance (TER) value was decreased in a dose dependent manner due to the markers of TJs occludin, claudin and zonula occludens-1 (ZO-1) expression decline...
January 4, 2018: Food and Chemical Toxicology
Sonia Chelouah, Emilie Cochet, Sophie Couvé, Sandy Balkaran, Aude Robert, Evelyne May, Vasily Ogryzko, Joëlle Wiels
The Epstein-Barr virus nuclear antigen leader protein (EBNA-LP) acts as a co-activator of EBNA-2, a transcriptional activator essential for Epstein-Barr virus (EBV)-induced B-cell transformation. Burkitt's lymphoma (BL) cells harboring a mutant EBV strain that lacks both the EBNA-2 gene and 3' exons of EBNA-LP express Y1Y2-truncated isoforms of EBNA-LP (tEBNA-LP) and better resist apoptosis than if infected with the wild-type virus. In such BL cells, tEBNA-LP interacts with the protein phosphatase 2A (PP2A) catalytic subunit (PP2A C), and this interaction likely plays a role in resistance to apoptosis...
January 5, 2018: Cancers
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...
January 4, 2018: Systems Biology in Reproductive Medicine
Felipe Schmitz, Paula Pierozan, Helena Biasibetti-Brendler, Fernanda Silva Ferreira, Fernanda Dos Santos Petry, Vera Maria Treis Trindade, Regina Pessoa-Pureur, Angela T S Wyse
Although methylphenidate (MPH) is ubiquitously prescribed to children and adolescents, the consequences of chronic utilization of this psychostimulant are poorly understood. In this study, we investigated the effects of MPH on cytoskeletal homeostasis and lipid content in rat hippocampus. Wistar rats received intraperitoneal injections of MPH (2.0 mg/kg) or saline solution (controls), once a day, from the 15th to the 44th day of age. Results showed that MPH provoked hypophosphorylation of glial fibrillary acidic protein (GFAP) and reduced its immunocontent...
December 29, 2017: Metabolic Brain Disease
Yuxia Jiao, Siqi Tan, Junyu Xiong
Sepsis is defined as life threatening organ dysfunction arising from a dysregulated host response to infection. The outcomes of sepsis include early mortality, delayed mortality and recovery, and depend on the inflammatory response. Previous studies have demonstrated that regulatory T cells (Tregs) are important in determining the outcome of sepsis, as their suppressive function serves a role in maintaining immune homeostasis. However, Treg-mediated immunosuppression during the course of sepsis remains unclear and little is known about the survival of patients following diagnosis...
December 2017: Experimental and Therapeutic Medicine
Hye-Jin Park, Kang-Woo Lee, Stephanie Oh, Run Yan, Jie Zhang, Thomas G Beach, Charles H Adler, Michael Voronkov, Steven P Braithwaite, Jeffry B Stock, M Maral Mouradian
Hyperphosphorylated tau aggregates are characteristic of tauopathies including progressive supranuclear palsy (PSP) and Alzheimer disease (AD), but factors contributing to pathologic tau phosphorylation are not well understood. Here, we studied the regulation of the major tau phosphatase, the heterotrimeric AB55αC protein phosphatase 2 A (PP2A), in PSP and AD. The assembly and activity of this PP2A isoform are regulated by reversible carboxyl methylation of its catalytic C subunit, while the B subunit confers substrate specificity...
December 21, 2017: Journal of Neuropathology and Experimental Neurology
Ha Ram Kang, Célio Junior da Costa Fernandes, Rodrigo Augusto da Silva, Vera Regina Leopoldo Constantino, Ivan Hong Jun Koh, Willian F Zambuzzi
The effect of LDH samples comprised of chloride anions intercalated between positive layers of magnesium/aluminum (Mg-Al LDH) or zinc/aluminum (Zn-Al LDH) chemical composition on pre-osteoblast performance is investigated. Non-cytotoxic concentrations of both LDHs modulated pre-osteoblast adhesion by triggering cytoskeleton rearrangement dependent on recruiting of Cofilin, which is modulated by the inhibition of the Protein Phosphatase 2A (PP2A), culminating in osteoblast differentiation with a significant increase of osteogenic marker genes...
December 27, 2017: Advanced Healthcare Materials
Geqi Cha, Jianyu Xu, Xiangying Xu, Bin Li, Shan Lu, Abiyasi Nanding, Songliu Hu, Shilong Liu
The aim of this work was to examine the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) in non-small cell lung cancer (NSCLC) and analyze its correlation with clinical outcomes. CIP2A protein levels were detected by immunohistochemistry (IHC). One hundred and eighty-four of 209 (88.3%) primary stage I-III NSCLC specimens and 4 of 38 (10.5%) adjacent normal lung tissue specimens expressed CIP2A protein. High expression of CIP2A was detected in 38.8% (81/209) of the NSCLC specimens. Patients diagnosed histologically with late-stage NSCLC (p<0...
2017: OncoTargets and Therapy
Kana Ishibashi, Kotaro Ishii, Goro Sugiyama, Y U Kamata, Azusa Suzuki, Wataru Kumamaru, Yukiko Ohyama, Hiroyuki Nakano, Tamotsu Kiyoshima, Tomoki Sumida, Tomohiro Yamada, Yoshihide Mori
BACKGROUND/AIM: Adenoid cystic carcinoma (AdCC) is a rare cancer of the salivary gland with high risk of recurrence and metastasis. Wnt signalling is critical for determining tumor grade in AdCC, as it regulates invasion and migration. β-catenin dephosphorylation plays an important role in the Wnt pathway, but its underlying molecular mechanism remains unclear. MATERIALS AND METHODS: Because the regulatory subunits of protein phosphatase 2A (PP2A) drive Wnt signalling via target molecules, including β-catenin, we used qRT-PCR and immunoblot analysis to investigate the expression of these subunits in an AdCC cell line (ACCS) and a more aggressive subline (ACCS-M)...
January 2018: Cancer Genomics & Proteomics
Ning Yu, TingGuo Zhang, DaHua Zhao, Zhang Cao, Jing Du, Qian Zhang
OBJECTIVE: Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a recently identified oncoprotein that stabilizes c-Myc and promotes cell proliferation and transformation. Here, we investigated the clinical significance and biological function of CIP2A in endometrial cancer. METHOD: CIP2A expression was assessed in normal endometrium, endometrial hyperplasia, endometrial atypical hyperplasia, and endometrioid adenocarcinoma tissues using immunohistochemistry, western blot, and RT-PCR...
November 15, 2017: Pathology, Research and Practice
Cheng-Guo Wu, Aiping Zheng, Li Jiang, Michael Rowse, Vitali Stanevich, Hui Chen, Yitong Li, Kenneth A Satyshur, Benjamin Johnson, Ting-Jia Gu, Zuojia Liu, Yongna Xing
Dynamic assembly/disassembly of signaling complexes are crucial for cellular functions. Specialized latency and activation chaperones control the biogenesis of protein phosphatase 2A (PP2A) holoenzymes that contain a common scaffold and catalytic subunits and a variable regulatory subunit. Here we show that the butterfly-shaped TIPRL (TOR signaling pathway regulator) makes highly integrative multibranching contacts with the PP2A catalytic subunit, selective for the unmethylated tail and perturbing/inactivating the phosphatase active site...
December 22, 2017: Nature Communications
Henan Zhao, Duojiao Li, Baojing Zhang, Yan Qi, Yunpeng Diao, Yuhong Zhen, Xiaohong Shu
Triple negative breast cancer (TNBC), is defined as a type of tumor lacking the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The ER, PR and HER2 are usually the molecular therapeutic targets for breast cancers, but they are ineffective for TNBC because of their negative expressions, so chemotherapy is currently the main treatment strategy in TNBC. However, drug resistance remains a major impediment to TNBC chemotherapeutic treatment. Recently, the protein phosphatase 2A (PP2A) has been found to regulate the phosphorylation of some substrates involved in the relevant target of TNBC, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may be the effective therapeutic strategies or influence drug sensitivity to TNBCs...
December 20, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Hongbo Du, Hao Yu, Yuying Yang, Yuanyuan Song, Fei Wang, Shangheng Li, Yuyong Jiang
Previous studies have revealed that the deregulation of circulating miRNAs is associated with liver cirrhosis. The present study aimed to identify reliable candidate biomarkers to improve the early detection of liver cirrhosis. An integrated analysis of expression profiles of microRNAs (miRNAs/miRs) and mRNAs in liver cirrhosis tissues from the GEO database was performed. Next, the regulatory targets of the differentially expressed miRNAs in liver cirrhosis tissues were predicted. In addition, a regulatory network of miRNA-target genes was constructed...
December 2017: Oncology Letters
Feng Guo, Nathan Wlodarchak, Patrick Menden, Yongna Xing
Proteomics is a powerful approach for systematic identification and quantification of the entire proteome of a biological system (cell, tissue, organ, biological fluid, or organism) at specific time points ( ). Extracting and purifying target proteins from native tissues are essential steps for many aspects of proteomic studies. In this chapter, we will introduce the experimental procedures to obtain soluble proteins from two different tissues: (1) the CCT (cpn-containing TCP-1) complex from bovine testes and (2) the protein phosphatase 2A (PP2A) catalytic subunit (PP2Ac or C) from porcine brains...
December 17, 2017: Methods in Molecular Biology
Xin Chen, Shanxiang Jiang
Maduramicin, a polyether ionophore antibiotic used as an anticoccidial agent in poultry industry, has been reported to be toxic to animals and humans if improperly used or by accident, resulting in heart failure, skeletal muscle degeneration and even death. However, the molecular mechanism underlying its cardiotoxicity remains elusive. Mitogen activated protein kinases (MAPKs) and protein phosphatases signaling pathways have been documented to be involved in the cell survival regulation. The present study was set to investigate the role of above pathways in maduramicin-induced myocardial cytotoxicity...
December 11, 2017: Toxicology Letters
Miklós Nagy, Sándor Kéki, Dávid Rácz, Jaideep Mathur, György Vereb, Tamás Garda, Márta M-Hamvas, François Chaumont, Károly Bóka, Béla Böddi, Csongor Freytag, Gábor Vasas, Csaba Máthé
The recently synthesized isocyanonaphtalene derivatives ACAIN and CACAIN are fluorochromes excitable at wavelengths of around 366 nm and bind cysteine-rich proteins with hydrophobic motifs. We show that these compounds preferentially label tonoplasts in living Arabidopsis and tobacco (Nicotiana tabacum SR1) cells. ACAIN-labeled membranes co-localized with the GFP signal in plants expressing GFP-δ-TIP (TIP2;1) (a tonoplast aquaporin) fusion protein. ACAIN preserved the dynamics of vacuolar structures. tip2;1 and triple tip1;1-tip1;2-tip2;1 knockout mutants showed weaker ACAIN signal in tonoplasts...
December 12, 2017: Protoplasma
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