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https://www.readbyqxmd.com/read/28343149/%C3%AE-adrenergic-stimulation-induces-histone-deacetylase-5-hdac5-nuclear-accumulation-in-cardiomyocytes-by-b55%C3%AE-pp2a-mediated-dephosphorylation
#1
Kate L Weeks, Antonella Ranieri, Agnieszka Karaś, Bianca C Bernardo, Alexandra S Ashcroft, Chris Molenaar, Julie R McMullen, Metin Avkiran
BACKGROUND: Class IIa histone deacetylase (HDAC) isoforms such as HDAC5 are critical signal-responsive repressors of maladaptive cardiomyocyte hypertrophy, through nuclear interactions with transcription factors including myocyte enhancer factor-2. β-Adrenoceptor (β-AR) stimulation, a signal of fundamental importance in regulating cardiac function, has been proposed to induce both phosphorylation-independent nuclear export and phosphorylation-dependent nuclear accumulation of cardiomyocyte HDAC5...
March 25, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28340282/carfilzomib-induces-leukaemia-cell-apoptosis-via-inhibiting-elk1-kiaa1524-elk-1-cip2a-and-activating-pp2a-not-related-to-proteasome-inhibition
#2
Chun-Yu Liu, Feng-Shu Hsieh, Pei-Yi Chu, Wen-Chun Tsai, Chun-Teng Huang, Yuan-Bin Yu, Tzu-Ting Huang, Po-Shen Ko, Man-Hsin Hung, Wan-Lun Wang, Chung-Wai Shiau, Kuen-Feng Chen
Enhancing the tumour suppressive activity of protein phosphatase 2A (PP2A) has been suggested to be an anti-leukaemic strategy. KIAA1524 (also termed CIP2A), an oncoprotein inhibiting PP2A, is associated with disease progression in chronic myeloid leukaemia and may be prognostic in cytogenetically normal acute myeloid leukaemia. Here we demonstrated that the selective proteasome inhibitor, carfilzomib, induced apoptosis in sensitive primary leukaemia cells and in sensitive leukaemia cell lines, associated with KIAA1524 protein downregulation, increased PP2A activity and decreased p-Akt, but not with the proteasome inhibition effect of carfilzomib...
March 24, 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/28330616/systematic-analysis-of-human-protein-phosphatase-interactions-and-dynamics
#3
Leena Yadav, Fitsum Tamene, Helka Göös, Audrey van Drogen, Riku Katainen, Ruedi Aebersold, Matthias Gstaiger, Markku Varjosalo
Coordinated activities of protein kinases and phosphatases ensure phosphorylation homeostasis, which, when perturbed, can instigate diseases, including cancer. Yet, in contrast to kinases, much less is known about protein phosphatase functions and their interactions and complexes. Here, we used quantitative affinity proteomics to assay protein-protein interactions for 54 phosphatases distributed across the three major protein phosphatase families, with additional analysis of their 12 co-factors. We identified 838 high-confidence interactions, of which 631, to our knowledge, have not been reported before...
March 15, 2017: Cell Systems
https://www.readbyqxmd.com/read/28329677/phd2-targeting-overcomes-breast-cancer-cell-death-upon-glucose-starvation-in-a-pp2a-b55%C3%AE-mediated-manner
#4
Giusy Di Conza, Sarah Trusso Cafarello, Xingnan Zheng, Qing Zhang, Massimiliano Mazzone
B55α is a regulatory subunit of the PP2A phosphatase. We have recently found that B55α-associated PP2A promotes partial deactivation of the HIF-prolyl-hydroxylase enzyme PHD2. Here, we show that, in turn, PHD2 triggers degradation of B55α by hydroxylating it at proline 319. In the context of glucose starvation, PHD2 reduces B55α protein levels, which correlates with MDA-MB231 and MCF7 breast cancer cell death. Under these conditions, PHD2 silencing rescues B55α degradation, overcoming apoptosis, whereas in SKBR3 breast cancer cells showing resistance to glucose starvation, B55α knockdown restores cell death and prevents neoplastic growth in vitro...
March 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28326019/nahs-protects-against-the-impairments-induced-by-oxygen-glucose-deprivation-in-different-ages-of-primary-hippocampal-neurons
#5
Qian Yu, Binrong Wang, Tianzhi Zhao, Xiangnan Zhang, Lei Tao, Jinshan Shi, Xude Sun, Qian Ding
Brain ischemia leads to poor oxygen supply, and is one of the leading causes of brain damage and/or death. Neuroprotective agents are thus in great need for treatment purpose. Using both young and aged primary cultured hippocampal neurons as in vitro models, we investigated the effect of sodium hydrosulfide (NaHS), an exogenous donor of hydrogen sulfide, on oxygen-glucose deprivation (OGD) damaged neurons that mimick focal cerebral ischemia/reperfusion (I/R) induced brain injury. NaHS treatment (250 μM) protected both young and aged hippocampal neurons, as indicated by restoring number of primary dendrites by 43...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28306189/map4k4-is-a-novel-mapk-erk-pathway-regulator-required-for-lung-adenocarcinoma-maintenance
#6
Xuan Gao, Guangming Chen, Chenxi Gao, Dennis Han Zhang, Shih-Fan Kuan, Laura P Stabile, Guoxiang Liu, Jing Hu
About 76% of lung adenocarcinoma patients harbor activating mutations in the receptor tyrosine kinase (RTK)/RAS/RAF pathways, leading to aberrant activation of the MAPK pathways particularly the MAPK/ERK pathway. However, many lung adenocarcinomas lacking these genomic mutations also display significant MAPK pathway activation, suggesting that additional MAPK pathway alterations remain undetected. This study has identified serine/threonine kinase mitogen-activated protein 4 kinase 4 (MAP4K4) as a novel positive regulator of MAPK/ERK signaling in lung adenocarcinoma...
March 17, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28300280/rapamycin-attenuates-baff-extended-proliferation-and-survival-via-disruption-of-mtorc1-2-signaling-in-normal-and-neoplastic-b-lymphoid-cells
#7
Qingyu Zeng, Shanshan Qin, Hai Zhang, Beibei Liu, Jiamin Qin, Xiaoxue Wang, Ruijie Zhang, Chunxiao Liu, Xiaoqing Dong, Shuangquan Zhang, Shile Huang, Long Chen
B cell activating factor from the TNF family (BAFF) stimulates B-cell proliferation and survival, but excessive BAFF promotes the development of aggressive B cells leading to malignant and autoimmune diseases. Recently, we have reported that rapamycin, a macrocyclic lactone, attenuates human soluble BAFF (hsBAFF)-stimulated B-cell proliferation/survival by suppressing mTOR-mediated PP2A-Erk1/2 signaling pathway. Here, we show that the inhibitory effect of rapamycin on hsBAFF-promoted B cell proliferation/survival is also related to blocking hsBAFF-stimulated phosphorylation of Akt, S6K1 and 4E-BP1, as well as expression of survivin in normal and B-lymphoid (Raji and Daudi) cells...
March 16, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28300193/interplay-of-myosin-phosphatase-and-protein-phosphatase-2a-in-the-regulation-of-endothelial-nitric-oxide-synthase-phosphorylation-and-nitric-oxide-production
#8
Róbert Bátori, Bálint Bécsi, Dénes Nagy, Zoltán Kónya, Csaba Hegedűs, Zsuzsanna Bordán, Alexander Verin, Beáta Lontay, Ferenc Erdődi
The inhibitory phosphorylation of endothelial nitric oxide (NO) synthase (eNOS) at Thr497 (eNOS(pThr497)) by protein kinase C or RhoA-activated kinase is a major regulatory determinant of eNOS activity. The signalling mechanisms involved in the dephosphorylation of eNOS(pThr497) have not yet been clarified. This study identifies myosin phosphatase (MP) holoenzyme consisting of protein phosphatase-1 catalytic subunit (PP1c) and MP target subunit-1 (MYPT1) as an eNOS(pThr497) phosphatase. In support of this finding are: (i) eNOS and MYPT1 interacts in various endothelial cells (ECs) and in in vitro binding assays (ii) MYPT1 targets and stimulates PP1c toward eNOS(pThr497) substrate (iii) phosphorylation of MYPT1 at Thr696 (MYPT1(pThr696)) controls the activity of MP on eNOS(pThr497)...
March 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28298211/fty720-inhibits-mesothelioma-growth-in-vitro-and-in-a-syngeneic-mouse-model
#9
Agata Szymiczek, Sandra Pastorino, David Larson, Mika Tanji, Laura Pellegrini, Jiaming Xue, Shuangjing Li, Carlotta Giorgi, Paolo Pinton, Yasutaka Takinishi, Harvey I Pass, Hideki Furuya, Giovanni Gaudino, Andrea Napolitano, Michele Carbone, Haining Yang
BACKGROUND: Malignant mesothelioma (MM) is a very aggressive type of cancer, with a dismal prognosis and inherent resistance to chemotherapeutics. Development and evaluation of new therapeutic approaches is highly needed. Immunosuppressant FTY720, approved for multiple sclerosis treatment, has recently raised attention for its anti-tumor activity in a variety of cancers. However, its therapeutic potential in MM has not been evaluated yet. METHODS: Cell viability and anchorage-independent growth were evaluated in a panel of MM cell lines and human mesothelial cells (HM) upon FTY720 treatment to assess in vitro anti-tumor efficacy...
March 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28283554/impaired-dual-specificity-protein-phosphatase-dusp4-reduces-corticosteroid-sensitivity
#10
Yoshiki Kobayashi, Kazuhiro Ito, Akira Kanda, Koich Tomoda, Nicolas Mercado, Peter Barnes
We have reported that phosphorylation of glucocorticoid receptor (GR) at Ser(226) reduces GR nuclear translocation resulting in corticosteroid insensitivity in patients with severe asthmas. A serine/threonine protein phosphatase, PP2A, which regulates JNK1 and GR-Ser(226) signaling, is involved in this mechanism. Here, we further explored dual-specificity protein kinases (DUSPs) with the ability to dephosphorylate JNK, and identified DUSP4 as a phosphatase involved in the regulation of corticosteroid sensitivity...
March 10, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28274314/-inhibitory-effect-of-magnesium-cantharidate-on-human-hepatoma-smmc-7721-cell-proliferation-by-blocking-mapk-signaling-pathway
#11
Yun Liu, Xiaofei Li, Qianqian Zou, Liu Liu, Xinting Zhu, Qi Jia, Lingjun Wang, Rong Yan
Objective To investigate the anticancer mechanism of magnesium cantharidate by observing its effect on the mitogen-activated protein kinase (MAPK) signaling pathway in human hepatoma SMMC-7721 cells. Methods The protein phosphatase 2A (PP2A) activity detection kit was used to detect the effects of magnesium cantharidate and okadaic acid (OA) on PP2A activity. After the treatment of SMMC-7721 cells with magnesium cantharidate and/or OA, mRNA levels of extracellular signal-regulated kinase 1 (ERK1), ERK2, p38MAPK, c-Jun N-terminal kinase 1 (JNK1) and JNK2 were detected by real-time quantitative PCR, and the protein expression levels and protein phosphorylation of ERK1, ERK2, p38 MAPK and JNK were determined by Western blotting...
March 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28267764/ex-vivo-modulation-of-the-foxo1-phosphorylation-state-does-not-lead-to-dysfunction-of-t-regulatory-cells
#12
Kristen Kelley Penberthy, Monica Weaver Buckley, Sanja Arandjelovic, Kodi Ravichandran
Peripheral regulatory CD4+ T cells (Treg cells) prevent maladaptive inflammatory responses to innocuous foreign antigens. Treg cell dysfunction has been linked to many inflammatory diseases, including allergic airway inflammation. Glucocorticoids that are used to treat allergic airway inflammation and asthma are thought to work in part by promoting Treg cell differentiation; patients who are refractory to these drugs have defective induction of anti-inflammatory Treg cells. Previous observations suggest that Treg cells deficient in the transcription factor FoxO1 are pro-inflammatory, and that FoxO1 activity is regulated by its phosphorylation status and nuclear localization...
2017: PloS One
https://www.readbyqxmd.com/read/28265764/germline-specific-labeling-of-the-somatic-chromosomes-by-protein-phosphatase-2a-and-histone-h3s28-phosphorylation-in-acricotopus-lucidus
#13
Wolfgang Staiber
Additional chromosomes limited to the germline (=Ks) were established as a special form of germline-soma differentiation in the Orthocladiinae, a subfamily of the Chironomidae (Bauer and Beermann in Z Naturforsch 7b: 557-563, 1952). The Ks together with the somatic chromosomes (=Ss) pass through a complex chromosome cycle with elimination at mitosis and a monopolar migration of all Ks. The dissimilar behavior of Ks and Ss in these exceptional mitoses initiated the search for differential chromosome marks in the orthocladiid Acricotopus lucidus...
March 6, 2017: Protoplasma
https://www.readbyqxmd.com/read/28265001/phosphorylated-nuclear-receptor-car-forms-a-homodimer-to-repress-its-constitutive-activity-for-ligand-activation
#14
Ryota Shizu, Makoto Osabe, Lalith Perera, Rick Moore, Tatsuya Sueyoshi, Masahiko Negishi
Nuclear receptor CAR (NR1I3) regulates hepatic drug and energy metabolism as well as cell fate. Its activation can be a critical factor in drug-induced toxicity and disease development such as diabetes and tumors. CAR inactivates its constitutive activity by phosphorylation at threonine 38. Utilizing receptor for protein kinase 1 (RACK1) as the regulatory subunit, protein phosphatase PP2A dephosphorylates threonine 38 to activate CAR. Here we have demonstrated that CAR undergoes its homodimer-monomer conversion to regulate this dephosphorylation...
March 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28259950/vinblastine-differs-from-taxol-as-it-inhibits-the-malignant-phenotypes-of-nsclc-cells-by-increasing-the-phosphorylation-of-op18-stathmin
#15
Fang Shen, Dan Long, Ting Yu, Xian Chen, Ying Liao, Yi Wu, Xuechi Lin
Taxol (paclitaxel) and vinblastine (VBL) are both efficacious chemotherapeutic agents that target the microtubules of tumor cells, but each functions in a mutual antagonistic manner. Op18/stathmin is a small molecular phosphoprotein which promotes depolymerization of microtubules. Non-small cell lung cancer (NSCLC) NCI-H1299 cells were employed to compare the curative effects of VBL and Taxol and explore the correlation between drug sensitivity and Op18/stathmin signaling. The present study found that VBL obviously promoted cellular apoptosis and initiated activation of caspase 3 and 9, and inhibited cell proliferation and colony formation, as well as cell migration in the NCI-H1299 cells in contrast with Taxol...
February 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28258923/cancer-associated-fibroblasts-promote-irradiated-cancer-cell-recovery-through-autophagy
#16
Yongbin Wang, Guifang Gan, Bocheng Wang, Jinliang Wu, Yuan Cao, Dan Zhu, Yan Xu, Xiaona Wang, Hongxiu Han, Xiaoling Li, Ming Ye, Jiangmin Zhao, Jun Mi
Tumor relapse after radiotherapy is a significant challenge to oncologists, even after recent the advances in technologies. Here, we showed that cancer-associated fibroblasts (CAFs), a major component of cancer stromal cells, promoted irradiated cancer cell recovery and tumor relapse after radiotherapy. We provided evidence that CAFs-produced IGF1/2, CXCL12 and β-hydroxybutyrate were capable of inducing autophagy in cancer cells post-radiation and promoting cancer cell recovery from radiation-induced damage in vitro and in vivo in mice...
February 22, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28251149/fibrillar-type-i-collagen-enhances-the-differentiation-and-proliferation-of-myofibroblasts-by-lowering-%C3%AE-2%C3%AE-1-integrin-expression-in-cardiac-fibrosis
#17
Jian Hong, Ming Chu, Lijun Qian, Junhong Wang, Yan Guo, Di Xu
Many studies have shown that α2β1 integrin plays an important role in the development of cardiac fibrosis. However, the mechanism of how α2β1 integrin regulates the differentiation and proliferation of myofibroblasts in cardiac fibrosis through fibrillar collagen (FC) remains uncertain. We established that FC mimicked the 3-dimensional extracellular matrix (ECM) of fibroblasts from post-myocardial infarction (MI) patients in vivo. This allowed us to explore the differentiation and proliferation of cardiac fibroblasts on FC...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28241801/the-protective-effects-of-propofol-against-cocl2-induced-ht22-cell-hypoxia-injury-via-pp2a-camkii%C3%AE-nnos-pathway
#18
Yan Lu, Wei Chen, Chen Lin, Jiaqiang Wang, Minmin Zhu, Jiawei Chen, Changhong Miao
BACKGROUND: Perioperative cerebral ischemia/hypoxia could induce hippocampal injury and has been reported to induce cognitive impairment. In this study, we used cobalt chloride (CoCl2) to build a hypoxia model in mouse hippocampal cell lines. Propofol, a widely used intravenous anesthetic agent, has been demonstrated to have neuroprotective effect. Here, we explored whether and how propofol attenuated CoCl2-induced mouse hippocampal HT22 cell injury. METHODS: Mouse hippocampal HT22 cells were pretreated with propofol, and then stimulated with CoCl2...
February 28, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28241467/role-of-protein-phosphatase-2a-in-osteoblast-differentiation-and-function
#19
REVIEW
Hirohiko Okamura, Kaya Yoshida, Hiroyuki Morimoto, Jumpei Teramachi, Kazuhiko Ochiai, Tatsuji Haneji, Akihito Yamamoto
The reversible phosphorylation of proteins plays hugely important roles in a variety of cellular processes, such as differentiation, proliferation, and apoptosis. These processes are strictly controlled by protein kinases (phosphorylation) and phosphatases (de-phosphorylation). Here we provide a brief history of the study of protein phosphorylation, including a summary of different types of protein kinases and phosphatases. One of the most physiologically important serine/threonine phosphatases is PP2A. This review provides a description of the phenotypes of various PP2A transgenic mice and further focuses on the known functions of PP2A in bone formation, including its role in osteoblast differentiation and function...
February 23, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28239848/protein-phosphatase-2a-pp2a-regulation-of-markers-of-extracellular-matrix-remodelling-in-hcc-cells-functional-consequences-for-tumour-invasion
#20
M P Ward, J P Spiers
BACKGROUND AND PURPOSE: A hallmark of tumour invasion is breakdown of the extracellular matrix as a consequence of dysregulation of the MMP system. While our understanding of how this is regulated by kinase signalling pathways is well established, its counter-regulation by protein phosphatases is less well known. Therefore, we investigated the effect of inhibition of protein phosphatases on markers of extracellular remodelling and how PP2A modulates MMP-9 abundance and function of Hep3B cells...
February 27, 2017: British Journal of Pharmacology
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