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Protein phosphatase 2a

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https://www.readbyqxmd.com/read/28548306/zanthoxylum-avicennae-extract-enhances-gsk-3%C3%AE-to-attenuate-%C3%AE-catenin-via-phosphatase-2a-to-block-metastatic-effects-of-ha22t-cells-and-hepatocellular-carcinoma-xenografted-nude-mice
#1
Hsi-Chin Wu, Ing-Shiow Lay, Marthandam Asokan Shibu, Tsung-Jung Ho, Shiu-Min Cheng, Chih-Hao Lin, Tran Duc Dung, Long-Bin Jeng, Vijaya Padma Viswanadha, Chih-Yang Huang
Hepatocellular carcinoma (HCC) metastasis is often associated with the activation of Wnt/β-catenin signaling pathway. Zanthoxylum avicennae (Ying Bu Bo, YBB), a traditional herb with hepatoprotective effect, has been proven to inhibit human HCC in in vivo models however, the in vitro and in vivo effect of YBB on tumor metastasis is not clear yet. To determine whether YBB could inhibit HA22T human HCC cell by acting on β-catenin metastatic signaling in vitro and in vivo, HA22T cells were treated with different concentrations of YBB extracts (YBBE) and analyzed by Immunofluorescence staining assay, western blot analysis, siRNA mediated gene knock-down assays and co-immunoprecipitation assay...
May 26, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28546021/sodium-butyrate-improved-intestinal-immune-function-associated-with-nf-%C3%AE%C2%BAb-and-p38mapk-signalling-pathways-in-young-grass-carp-ctenopharyngodon-idella
#2
Li Tian, Xiao-Qiu Zhou, Wei-Dan Jiang, Yang Liu, Pei Wu, Jun Jiang, Sheng-Yao Kuang, Ling Tang, Wu-Neng Tang, Yong-An Zhang, Fei Xie, Lin Feng
The present study evaluated the effect of dietary sodium butyrate (SB) supplementation on the growth and immune function in the proximal intestine (PI), middle intestine (MI) and distal intestine (DI) of young grass carp (Ctenopharyngodon idella). The fish were fed one powdery sodium butyrate (PSB) diet (1000.0 mg kg(-1) diet) and five graded levels of microencapsulated sodium butyrate (MSB) diets: 0.0 (control), 500.0, 1000.0, 1500.0 and 2000.0 mg kg(-1) diet for 60 days. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila...
May 22, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28543283/targeting-pp2a-and-proteasome-activity-ameliorates-features-of-allergic-airway-disease-in-mice
#3
Prema M Nair, Malcolm R Starkey, Tatt Jhong Haw, Gang Liu, Jay C Horvat, Jonathan C Morris, Nikki M Verrills, Andrew R Clark, Alaina J Ammit, Philip M Hansbro
BACKGROUND: Asthma is an allergic airway disease (AAD) caused by aberrant immune responses to allergens. Protein phosphatase-2A (PP2A) is an abundant serine/threonine phosphatase with anti-inflammatory activity. The ubiquitin proteasome system (UPS) controls many cellular processes, including the initiation of inflammatory responses by protein degradation. We assessed if enhancing PP2A activity with Fingolimod (FTY720) or 2-amino-4-(4-(heptyloxy) phenyl)-2-methylbutan-1-ol (AAL(S) ), or inhibiting proteasome activity with Bortezomib (BORT) could suppress experimental AAD...
May 24, 2017: Allergy
https://www.readbyqxmd.com/read/28534965/cucurbitacin%C3%A2-b-induces-autophagy-and-apoptosis-by-suppressing-cip2a-pp2a-mtorc1-signaling-axis-in-human-cisplatin-resistant-gastric-cancer-cells
#4
Xuewen Liu, Chao Duan, Juanli Ji, Te Zhang, Xiaoning Yuan, Yunfei Zhang, Wenjing Ma, Jingyuan Yang, Linsen Yang, Zhiguo Jiang, Huiliang Yu, Ying Liu
Cancerous inhibitor of protein phosphatase 2A (CIP2A) is a human oncoprotein that is overexpressed in multiple kinds of tumors including gastric cancer (GC). Mammalian target of rapamycin complex 1 (mTORC1) over-activation is detected in GC and many other cancers. Previous study found that CIP2A/mTORC1 controls cell growth and autophagy through direct association. CIP2A plays an 'oncogenic nexus' in several cancer types to participate in the tumorigenic transformation and chemoresistance. In the present study, we investigated whether Cucurbitacin B (CuB), a natural compound found in Cucurbitaceae, can be used in cisplatin (DDP)-resistant human GC cell line SGC7901/DDP...
May 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28526910/expression-and-regulation-of-type-2a-protein-phosphatases-and-alpha4-signalling-in-cardiac-health-and-hypertrophy
#5
Olga Eleftheriadou, Andrii Boguslavskyi, Michael R Longman, Jonathan Cowan, Asvi Francois, Richard J Heads, Brian E Wadzinski, Ali Ryan, Michael J Shattock, Andrew K Snabaitis
Cardiac physiology and hypertrophy are regulated by the phosphorylation status of many proteins, which is partly controlled by a poorly defined type 2A protein phosphatase-alpha4 intracellular signalling axis. Quantitative PCR analysis revealed that mRNA levels of the type 2A catalytic subunits were differentially expressed in H9c2 cardiomyocytes (PP2ACβ > PP2ACα > PP4C > PP6C), NRVM (PP2ACβ > PP2ACα = PP4C = PP6C), and adult rat ventricular myocytes (PP2ACα > PP2ACβ > PP6C > PP4C)...
July 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28526544/interleukin-18-gene-deletion-protects-against-sepsis-induced-cardiac-dysfunction-by-inhibiting-pp2a-activity
#6
Yoshitaka Okuhara, Shunichi Yokoe, Toshihiro Iwasaku, Akiyo Eguchi, Koichi Nishimura, Wen Li, Makiko Oboshi, Yoshiro Naito, Toshiaki Mano, Michio Asahi, Haruki Okamura, Tohru Masuyama, Shinichi Hirotani
BACKGROUND: Interleukin-18 (IL-18) neutralization protects against lipopolysaccharide (LPS)-induced injuries, including myocardial dysfunction. However, the mechanism is yet to be fully elucidated. The aim of the present study was to determine whether IL-18 gene deletion prevents sepsis-induced cardiac dysfunction and to elucidate the potential mechanisms underlying IL-18-mediated cardiotoxicity by LPS. METHODS AND RESULTS: Ten-week-old male wild-type (WT) and IL-18 knockout (IL-18 KO) mice were intraperitoneally administered LPS...
May 4, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28521777/cip2a-mediates-fibronectin-induced-bladder-cancer-cell-proliferation-by-stabilizing-%C3%AE-catenin
#7
Fengbin Gao, Tianyuan Xu, Xianjin Wang, Shan Zhong, Shanwen Chen, Minguang Zhang, Xiaohua Zhang, Yifan Shen, Xiaojing Wang, Chen Xu, Zhoujun Shen
BACKGROUND: Fibronectin (FN) is associated with tumorigenesis and progression in bladder cancer, however, the underlying mechanisms causing this remain largely unknown. Furthermore, cancerous inhibitor of protein phosphatase 2A (CIP2A) has been shown to play important regulatory roles in cancer proliferation. Here, we investigated whether FN regulates CIP2A expression to promote bladder cancer cell proliferation. METHODS: The correlations of stromal FN with CIP2A and proliferating cell nuclear antigen (PCNA) expression were analyzed in a cohort bladder cancer patients...
May 18, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28516459/pp2a-deactivation-is-a-common-event-in-oral-cancer-and-reactivation-by-fty720-shows-promising-therapeutic-potential
#8
Bharath Kumar Velmurugan, Chien-Hung Lee, Shang-Lun Chiang, Chun-Hung Hua, Mei-Chung Chen, Shu-Hui Lin, Kun-Tu Yeh, Ying-Chin Ko
Protein phosphatase 2A (PP2A) is a tumor suppressor gene, that has been frequently deactivated in many types of cancer. However its molecular and clinical relevance in oral squamous cell carcinoma (OSCC) remain unclear. Here we show that, PP2A deactivation is a common event in oral cancer cells and hyperphosphorylation in its tyrosine-307 (Y307) residue contributes to PP2A deactivation. PP2A restoration by FTY720 treatment reduced cell growth and decreased GSK-3β phosphorylation without significantly altering other PP2A targets...
May 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28504652/a-smap-in-the-face-for-cancer
#9
Shirish Shenolikar
Observed deficits in protein phosphatase 2A (PP2A) function in a variety of human cancers have stimulated drug discovery efforts aimed at restoring PP2A function to inhibit tumor growth. Work published by Sangodkar et al. in this issue of the JCI describes the characterization of orally available small molecule activators of PP2A (SMAPs). These SMAPs attenuated mitogenic signaling and triggered apoptosis in KRAS-mutant lung cancer cells and inhibited tumor growth in murine models. Tumors with mutations in the SMAP-binding site of the PP2A A subunit displayed resistance to SMAPs...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28504649/activation-of-tumor-suppressor-protein-pp2a-inhibits-kras-driven-tumor-growth
#10
Jaya Sangodkar, Abbey Perl, Rita Tohme, Janna Kiselar, David B Kastrinsky, Nilesh Zaware, Sudeh Izadmehr, Sahar Mazhar, Danica D Wiredja, Caitlin M O'Connor, Divya Hoon, Neil S Dhawan, Daniela Schlatzer, Shen Yao, Daniel Leonard, Alain C Borczuk, Giridharan Gokulrangan, Lifu Wang, Elena Svenson, Caroline C Farrington, Eric Yuan, Rita A Avelar, Agnes Stachnik, Blake Smith, Vickram Gidwani, Heather M Giannini, Daniel McQuaid, Kimberly McClinch, Zhizhi Wang, Alice C Levine, Rosalie C Sears, Edward Y Chen, Qiaonan Duan, Manish Datt, Shozeb Haider, Avi Ma'ayan, Analisa DiFeo, Neelesh Sharma, Matthew D Galsky, David L Brautigan, Yiannis A Ioannou, Wenqing Xu, Mark R Chance, Michael Ohlmeyer, Goutham Narla
Targeted cancer therapies, which act on specific cancer-associated molecular targets, are predominantly inhibitors of oncogenic kinases. While these drugs have achieved some clinical success, the inactivation of kinase signaling via stimulation of endogenous phosphatases has received minimal attention as an alternative targeted approach. Here, we have demonstrated that activation of the tumor suppressor protein phosphatase 2A (PP2A), a negative regulator of multiple oncogenic signaling proteins, is a promising therapeutic approach for the treatment of cancers...
May 15, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28502066/ebselen-ameliorates-%C3%AE-amyloid-pathology-tau-pathology-and-cognitive-impairment-in-triple-transgenic-alzheimer-s-disease-mice
#11
Yongli Xie, Yibin Tan, Youbiao Zheng, Xiubo Du, Qiong Liu
Alzheimer's disease (AD) is a progressive neurodegenerative disease which is clinically characterized by memory loss and cognitive decline caused by protein misfolding and aggregation. Imbalance between free radicals and the antioxidant system is a prominent and early feature in the neuropathology of AD. Selenium (Se), a vital trace element with excellent antioxidant potential, is preferentially retained in the brain in Se-limited conditions and has been reported to provide neuroprotection through resisting oxidative damage...
May 13, 2017: Journal of Biological Inorganic Chemistry: JBIC
https://www.readbyqxmd.com/read/28500640/dysregulation-of-the-mek-erk-mnk1-signaling-cascade-by-middle-t-antigen-of-the-trichoydsplasia-spinulosa-polyomavirus
#12
Julie H Wu, Deepika Narayanan, Rebecca A Simonette, Peter L Rady, Stephen 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 tumor (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
https://www.readbyqxmd.com/read/28497395/cardio-protective-effects-of-qishen-granule-on-sarcoplasmic-reticulum-ca-2-handling-in-heart-failure-rats
#13
Ling-Hui Lu, Chun Li, Qi-Yan Wang, Qian Zhang, Yi Zhang, Hui Meng, Yong Wang, Wei Wang
OBJECTIVES: To assess the effects of Qishen Granule (, QSG) on sarcoplasmic reticulum (SR) Ca(2+) handling in heart failure (HF) model of rats and to explore the underlying molecular mechanisms. METHODS: HF rat models were induced by left anterior descending coronary artery ligation surgery and high-fat diet feeding. Rats were randomly divided into sham (n=10), model (n=10), QSG (n=12, 2.2 g/kg daily) and metoprolol groups (n=12, 10.5 mg/kg daily). The therapeutic effects of QSG were evaluated by echocardiography and blood lipid testing...
May 11, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28487562/protein-phosphatase-2a-pp2a-regulates-eg5-to-control-mitotic-progression
#14
Yang Liu, Zhong Zhang, Hui Liang, Xuyang Zhao, Ling Liang, Guangxi Wang, Jingyi Yang, Yan Jin, Michael A McNutt, Yuxin Yin
EG5 (KIF11) is a member of the kinesin-like protein family involved in centrosome separation and bipolar spindle formation. When a cell enters mitosis, CDK1 phosphorylates EG5 at Thr926 and promotes EG5 localization on the mitotic spindle which drives bipolar spindle formation. EG5 provides power for spindle movement and thus controls the dynamics of spindle assembly. However, little is known about EG5 regulation or how EG5 detaches from the spindle upon mitotic exit. In this study we identify EG5 as a novel substrate of PP2A phosphatase, and we show that the PP2A/B55α complex plays an important role in mitotic exit by a mechanism involving EG5...
May 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28484102/the-role-of-protein-phosphatase-2a-in-inflammation-and-cancer
#15
Shuhei Enjoji, Takashi Ohama
No abstract text is available yet for this article.
2017: Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica
https://www.readbyqxmd.com/read/28483815/drosophila-dalmatian-combines-sororin-and-shugoshin-roles-in-establishment-and-protection-of-cohesion
#16
Takashi Yamada, Eri Tahara, Mai Kanke, Keiko Kuwata, Tomoko Nishiyama
Sister chromatid cohesion is crucial to ensure chromosome bi-orientation and equal chromosome segregation. Cohesin removal via mitotic kinases and Wapl has to be prevented in pericentromeric regions in order to protect cohesion until metaphase, but the mechanisms of mitotic cohesion protection remain elusive in Drosophila Here, we show that dalmatian (Dmt), an ortholog of the vertebrate cohesin-associated protein sororin, is required for protection of mitotic cohesion in flies. Dmt is essential for cohesion establishment during interphase and is enriched on pericentromeric heterochromatin...
May 8, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28459461/mir-181b-modulates-egfr-dependent-vcam-1-expression-and-monocyte-adhesion-in-glioblastoma
#17
Y-S Liu, H-Y Lin, S-W Lai, C-Y Huang, B-R Huang, P-Y Chen, K-C Wei, D-Y Lu
Tumor-associated macrophages (TAMs) originate as circulating monocytes, and are recruited to gliomas, where they facilitate tumor growth and migration. Understanding the interaction between TAM and cancer cells may identify therapeutic targets for glioblastoma multiforme (GBM). Vascular cell adhesion molecule-1 (VCAM-1) is a cytokine-induced adhesion molecule expressed on the surface of cancer cells, which is involved in interactions with immune cells. Analysis of the glioma patient database and tissue immunohistochemistry showed that VCAM-1 expression correlated with the clinico-pathological grade of gliomas...
May 1, 2017: Oncogene
https://www.readbyqxmd.com/read/28448624/overexpression-of-the-protein-phosphatase-2a-regulatory-subunit-a-gene-zmpp2aa1-improves-low-phosphate-tolerance-by-remodeling-the-root-system-architecture-of-maize
#18
Jiemin Wang, Laming Pei, Zhe Jin, Kewei Zhang, Juren Zhang
Phosphate (Pi) limitation is a constraint for plant growth and development in many natural and agricultural ecosystems. In this study, a gene encoding Zea mays L. protein phosphatase 2A regulatory subunit A, designated ZmPP2AA1, was induced in roots by low Pi availability. The function of the ZmPP2AA1 gene in maize was analyzed using overexpression and RNA interference. ZmPP2AA1 modulated root gravitropism, negatively regulated primary root (PR) growth, and stimulated the development of lateral roots (LRs)...
2017: PloS One
https://www.readbyqxmd.com/read/28445932/high-cftr-expression-in-philadelphia-chromosome-positive-acute-leukemia-protects-and-maintains-continuous-activation-of-bcr-abl-and-related-signaling-pathways-in-combination-with-pp2a
#19
Xi Yang, Tianyou Yan, Yuping Gong, Xuehua Liu, Huaqin Sun, Wenming Xu, Chunsen Wang, Duolan Naren, Yuhuan Zheng
Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ domain, CFTR is capable of regulating other proteins, such as protein phosphatase 2A (PP2A). The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28439046/protein-phosphatase-2a-regulatory-subunit-b55%C3%AE-functions-in-mouse-oocyte-maturation-and-early-embryonic-development
#20
Shuang Liang, Jing Guo, Jeong-Woo Choi, Kyung-Tae Shin, Hai-Yang Wang, Yu-Jin Jo, Nam-Hyung Kim, Xiang-Shun Cui
Protein phosphatase 2A regulatory subunit B55α (PP2A-B55α) has been studied in mitosis. However, its functions in mammalian meiosis and early embryonic development remain unknown. Here, we report that PP2A-B55α is critical for mouse oocyte meiosis and preimplantation embryo development. Knockdown of PP2A-B55α in oocytes led to abnormal asymmetric division, disordered spindle dynamics, defects in chromosome congression, an increase in aneuploidy, and induction of the DNA damage response. Moreover, knockdown of PP2A-B55α in fertilized mouse zygotes impaired development to the blastocyst stage...
April 18, 2017: Oncotarget
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