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Pp2a

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https://www.readbyqxmd.com/read/29774021/mitotic-spindle-organizing-protein-mzta-mediates-septation-signaling-by-suppressing-the-regulatory-subunit-of-protein-phosphatase-2a-para-in-aspergillus-nidulans
#1
Ping Jiang, Shujun Zheng, Ling Lu
The proper timing and positioning of cytokinesis/septation is crucial for hyphal growth and conidiation in Aspergillus nidulans . The septation initiation network (SIN) components are a conserved spindle pole body (SPB) localized signaling cascade and the terminal kinase complex SidB-MobA, which must localize on the SPB in this pathway to trigger septation/cytokinesis. The regulatory subunit of phosphatase PP2A-ParA has been identified to be a negative regulator capable of inactivating the SIN. However, little is known about how ParA regulates the SIN pathway and whether ParA regulates the septum formation process through affecting the SPB-localized SIN proteins...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29764860/membrane-initiated-estrogen-receptor-signaling-mediates-metabolic-homeostasis-via-central-activation-of-protein-phosphatase-2a
#2
Kazutaka Ueda, Eiki Takimoto, Qing Lu, Pangyen Liu, Nobuaki Fukuma, Yusuke Adachi, Ryo Suzuki, Shengpu Chou, Wendy Baur, Mark J Aronovitz, Andrew S Greenberg, Issei Komuro, Richard H Karas
Women gain weight and their diabetes risk increases as they transition through menopause; these changes can in part be reversed by hormone therapy. However, the underlying molecular mechanisms mediating these effects are unknown. A novel knock-in mouse line with the selective blockade of the membrane-initiated estrogen receptor (ER) pathway was employed, and we found that the lack of this pathway precipitated excessive weight gain and glucose intolerance independent of food intake, and that this was accompanied by impaired adaptive thermogenesis and reduced physical activity...
May 15, 2018: Diabetes
https://www.readbyqxmd.com/read/29760653/ck2-phosphorylating-i-2-pp2a-set-mediates-tau-pathology-and-cognitive-impairment
#3
Qing Zhang, Yiyuan Xia, Yongjun Wang, Yangping Shentu, Kuan Zeng, Yacoubou A R Mahaman, Fang Huang, Mengjuan Wu, Dan Ke, Qun Wang, Bin Zhang, Rong Liu, Jian-Zhi Wang, Keqiang Ye, Xiaochuan Wang
Casein kinase 2 (CK2) is highly activated in Alzheimer disease (AD) and is associated with neurofibrillary tangles formation. Phosphorylated SET, a potent PP2A inhibitor, mediates tau hyperphosphorylation in AD. However, whether CK2 phosphorylates SET and regulates tau pathological phosphorylation in AD remains unclear. Here, we show that CK2 phosphorylating SET at Ser9 induced tau hyperphosphorylation in AD. We found that either Aβ treatment or tau overexpression stimulated CK2 activation leading to SET Ser9 hyperphosphorylation in neurons and animal models, while inhibition of CK2 by TBB abolished this event...
2018: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29752834/h-2-o-2-induces-pp2a-demethylation-to-downregulate-mtorc1-signaling-in-hek293-cells
#4
Shen Tang, Fu Qin, Xinhang Wang, Ziwei Liang, Haiqing Cai, Laiming Mo, Yue Huang, Boyin Liang, Xuejing Wei, Qingqing Ao, Yilu Xu, Yuyang Liu, Deqiang Xiao, Songchao Guo, Cailing Lu, Xiyi Li
Mammalian target of rapamycin (mTOR) is a Ser/Thr protein kinase that functions as an ATP and amino acid sensor to govern cell growth and proliferation by mediating mitogen- and nutrient-dependent signal transduction. Protein phosphatase 2A (PP2A), a ubiquitously expressed serine/threonine phosphatase, negatively regulates mTOR signaling. Methylation of PP2A is catalyzed by leucine carboxyl methyltransferase-1 (LCMT1) and reversed by protein phosphatase methylesterase 1 (PME-1), which regulates PP2A activity and substrate specificity...
May 12, 2018: Cell Biology International
https://www.readbyqxmd.com/read/29747346/-phenotype-and-mechanism-of-inducible-ppp2r1a-knockout-mouse-model
#5
J L Fan, F P Wang, S Wang, X L Liu, X N Wu, W Chen, L P Chen, W X Li
Objective: Investigate the effects of inducible ppp2r1a knockout on main physiological function in adult mice and study the mechanism. Methods: Ppp2r1a(flox/flox) mice and CAGG-CreER mice were hybridized to obtain 20 CAGG-CreER ppp2r1a(flox/flox) and 20 mice in homozygous group. Two groups of mice were divided into 4 groups respectively, finally we got 8 groups with 5 mice in each group. Tamoxifen was injected intraperitoneally to acquire inducible ppp2r1a knockout mice. The knockout efficiency of PP2A Aα in vital organs was measured by Western blot...
May 6, 2018: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
https://www.readbyqxmd.com/read/29743597/mastl-overexpression-promotes-chromosome-instability-and-metastasis-in-breast-cancer
#6
Samuel Rogers, Rachael A McCloy, Benjamin L Parker, David Gallego-Ortega, Andrew M K Law, Venessa T Chin, James R W Conway, Dirk Fey, Ewan K A Millar, Sandra O'Toole, Niantao Deng, Alexander Swarbrick, Paul D Chastain, Anthony J Cesare, Paul Timpson, C Elizabeth Caldon, David R Croucher, David E James, D Neil Watkins, Andrew Burgess
MASTL kinase is essential for correct progression through mitosis, with loss of MASTL causing chromosome segregation errors, mitotic collapse and failure of cytokinesis. However, in cancer MASTL is most commonly amplified and overexpressed. This correlates with increased chromosome instability in breast cancer and poor patient survival in breast, ovarian and lung cancer. Global phosphoproteomic analysis of immortalised breast MCF10A cells engineered to overexpressed MASTL revealed disruption to desmosomes, actin cytoskeleton, PI3K/AKT/mTOR and p38 stress kinase signalling pathways...
May 10, 2018: Oncogene
https://www.readbyqxmd.com/read/29735529/global-loss-of-leucine-carboxyl-methyltransferase-1-causes-severe-defects-in-fetal-liver-hematopoiesis
#7
Jocelyn A Lee, Zhengqi Wang, Danielle Sambo, Kevin D Bunting, David C Pallas
Leucine Carboxyl Methyltransferase-1 (LCMT-1)3 methylates the carboxy-terminal leucine α-carboxyl group of the catalytic subunits of the protein phosphatase 2A (PP2A) subfamily of protein phosphatases, PP2Ac, PP4c, and PP6c. LCMT-1 differentially regulates the formation and function of a subset of the heterotrimeric complexes that PP2A and PP4 form with their regulatory subunits. Global LCMT-1 knockout causes embryonic lethality in mice, but LCMT-1 function in development is unknown. In the current study, we analyzed the effects of global LCMT-1 loss on embryonic development...
May 7, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29723508/inhibition-of-pp2a-by-hesperetin-contributes-to-akt-and-erk1-2-activation-in-primary-cortical-neurons
#8
David Vauzour, Simone Corsini, Michael Müller, Jeremy P E Spencer
Flavonoids and their metabolites are well reported to modulate the activation/phosphorylation of various cellular kinases, such as ERK1/2 and JNK, although the mechanism by which they do so is unclear. In this study, we investigated the impact of flavanones on the activation of PI3K/Akt and ERK1/2 and determine whether this is mediated, in part, by the inhibition of phosphatases. Primary cortical neurons were exposed to physiological concentrations of hesperetin and the phosphorylation status of the kinases PI3K/Akt and ERK1/2 and the phosphatases PP2A and PTEN were assessed by immunoblotting after 30 min...
April 30, 2018: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/29721551/investigating-the-role-of-rts1-in-dna-replication-initiation
#9
Ana B A Wallis, Conrad A Nieduszynski
Background: Understanding DNA replication initiation is essential to understand the mis-regulation of replication seen in cancer and other human disorders. DNA replication initiates from DNA replication origins. In eukaryotes, replication is dependent on cell cycle kinases which function during S phase. Dbf4-dependent kinase (DDK) and cyclin-dependent kinase (CDK) act to phosphorylate the DNA helicase (composed of mini chromosome maintenance proteins: Mcm2-7) and firing factors to activate replication origins...
2018: Wellcome Open Research
https://www.readbyqxmd.com/read/29721191/microrna-652-induces-ned-in-lncap-and-emt-in-pc3-prostate-cancer-cells
#10
Robert K Nam, Tania Benatar, Yutaka Amemiya, Christopher J D Wallis, Joan Miguel Romero, Melina Tsagaris, Christopher Sherman, Linda Sugar, Arun Seth
MicroRNAs (miRNAs) are small noncoding RNA molecules that post-transcriptionally regulate gene expression. Dysregulation of miRNAs is frequently associated with disease and, in particular, is involved in prostate cancer progression. Next generation miRNA sequencing identified a panel of five miRNAs associated with prostate cancer recurrence and metastasis. High expression of one of these five miRNAs, miR-652, correlated significantly with an increased rate of prostate cancer biochemical recurrence. Overexpression of miR-652 in prostate cancer cells, PC3 and LNCaP, resulted in increased growth, migration and invasion...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29720672/fty720-decreases-tumorigenesis-in-group-3-medulloblastoma-patient-derived-xenografts
#11
Evan F Garner, Adele P Williams, Laura L Stafman, Jamie M Aye, Elizabeth Mroczek-Musulman, Blake P Moore, Jerry E Stewart, Gregory K Friedman, Elizabeth A Beierle
Group 3 tumors account for 28% of medulloblastomas and have the worst prognosis. FTY720, an immunosuppressant currently approved for treatment of multiple sclerosis, has shown antitumor effects in several human cancer cell lines. We hypothesized that treatment with FTY720 (fingolimod) would decrease tumorigenicity in medulloblastoma patient-derived xenografts (PDXs). Three Group 3 medulloblastoma PDXs (D341, D384 and D425) were utilized. Expression of PP2A and its endogenous inhibitors I2PP2A and CIP2A was detected by immunohistochemistry and immunoblotting...
May 2, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29706648/transient-pp2a-inhibition-alleviates-normal-tissue-stem-cell-susceptibility-to-cell-death-during-radiotherapy
#12
Maria Rita Fabbrizi, Barbara Meyer, Sandeep Misri, Suyash Raj, Cheri L Zobel, Dennis E Hallahan, Girdhar G Sharma
Unintended outcomes of cancer therapy include ionizing radiation (IR)-induced stem cell depletion, diminished regenerative capacity, and accelerated aging. Stem cells exhibit attenuated DNA damage response (DDR) and are hypersensitive to IR, as compared to differentiated non-stem cells. We performed genomic discovery research to compare stem cells to differentiated cells, which revealed Phosphoprotein phosphatase 2A (PP2A) as a potential contributor to susceptibility in stem cells. PP2A dephosphorylates pATM, γH2AX, pAkt etc...
April 30, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29704550/tau-hyperphosphorylation-and-p-creb-reduction-are-involved-in-acrylamide-induced-spatial-memory-impairment-suppression-by-curcumin
#13
Dandan Yan, Jianling Yao, Ying Liu, Xing Zhang, Yiqi Wang, Xiaoyi Chen, Liegang Liu, Nian Shi, Hong Yan
Acrylamide (ACR) is an axonal toxicant that produces peripheral neuropathy in laboratory animals and humans. Epidemiological study found that diet ACR exposure was associated with a mild cognitive decline in men. However, limited information is available as regards its potential and underlying mechanism to cause memory alterations. Curcumin is a polyphenol with neuroprotective and cognitive-enhancing properties. In this study, we aimed to investigate the mechanism of ACR-induced spatial memory impairment and the beneficial effect of curcumin...
April 26, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29703716/cip2a-and-setbp1-mediated-pp2a-inhibition-reveals-akt-s473-phosphorylation-to-be-a-new-biomarker-in-aml
#14
Claire M Lucas, Laura J Scott, Natasha Carmell, Alison K Holcroft, Robert K Hills, Alan K Burnett, Richard E Clark
No abstract text is available yet for this article.
May 8, 2018: Blood Advances
https://www.readbyqxmd.com/read/29702193/mir-19a-mediated-downregulation-of-rhob-inhibits-the-dephosphorylation-of-akt1-and-induces-osteosarcoma-cell-metastasis
#15
Qingping Zou, Xin Xiao, Ying Liang, Lina Peng, Zheng Guo, Wei Li, Wenqiang Yu
Osteosarcoma is a primary malignancy that develops in bone, along with serious recurrence and metastasis. As an isoform of Rho family GTPases, RhoB could suppress cell proliferation, invasion, and anti-angiogenesis. But it is not clear how RhoB involves in tumor metastasis. Here we found that expression of RhoB was decreased in osteosarcoma primary samples and cell lines. Ectopic expression of RhoB restrains the migration of osteosarcoma cells in vitro and in vivo, and induces osteosarcoma cell apopotsis. Further study showed that RhoB could interact with B55, increase the proportion of B55 in PP2A complex, and then enhance the dephosphorylation of AKT1...
April 24, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29693750/protein-phosphatase-2a-mediates-js-k-induced-apoptosis-by-affecting-bcl-2-family-proteins-in-human-hepatocellular-carcinoma-hepg2-cells
#16
Ling Liu, Zile Huang, Jingjing Chen, Jiangang Wang, Shuying Wang
Protein phosphatase 2A (PP2A) is an important enzyme within various signal transduction pathways. The present study was investigated PP2A mediates JS-K-induced apoptosis by affecting Bcl-2 family protein. JS-K showed diverse inhibitory effects in five HCC cell lines, especially HepG2 cells. JS-K caused a dose- and time-dependent reduction in cell viability and increased in levels of LDH release. Meanwhile, JS-K- induced apoptosis was characterized by mitochondrial membrane potential reduction, Hoechst 33342+ /PI+ dual staining, release of cytochrome c (Cyt c), and activation of cleaved caspase-9/3...
April 25, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29689717/mechanism-of-tau-hyperphosphorylation-involving-lysosomal-enzyme-asparagine-endopeptidase-in-a-mouse-model-of-brain-ischemia
#17
Gustavo Basurto-Islas, Jin-Hua Gu, Yunn Chyn Tung, Fei Liu, Khalid Iqbal
Dementias including Alzheimer's disease (AD) are multifactorial disorders that involve several different etiopathogenic mechanisms. Cerebral ischemia has been suspected in the altered regulation of protein kinases and phosphatases that leads to hyperphosphorylation of tau and further neurofibrillary pathology, a key hallmark of AD and related neurodegenerative diseases. However, the deregulation of these enzymes and their relationship with ischemia and AD remain unclear. Previously, we reported a mechanism by which the lysosomal enzyme asparagine endopeptidase (AEP) is associated with brain acidosis and AD...
April 14, 2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29688618/se-methylselenocysteine-ameliorates-neuropathology-and-cognitive-deficits-by-attenuating-oxidative-stress-and-metal-dyshomeostasis-in-alzheimer-model-mice
#18
Yongli Xie, Qiong Liu, Lin Zheng, BingTao Wang, Xiaogang Qu, Jiazuan Ni, Yan Zhang, Xiubo Du
SCOPE: Se-methylselenocysteine (SMC) is a major selenocompound in selenium (Se) enriched plants such as garlic and broccoli florets. Se is vital for proper brain function, and Se-deficient is considered to be related with cognitive impairment and Alzheimer's disease (AD). In this study, we evaluated for the first time the potential of SMC in intervening cognitive deficits and neuropathology of triple transgenic AD (3 × Tg-AD) mice. METHODS AND RESULTS: AD mice were treated with SMC (0...
April 24, 2018: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29688323/silac-based-phosphoproteomics-reveals-new-pp2a-cdc55-regulated-processes-in-budding-yeast
#19
Barbara Baro, Soraya Játiva, Inés Calabria, Judith Vinaixa, Joan-Josep Bech-Serra, Carolina de LaTorre, João Rodrigues, María Luisa Hernáez, Concha Gil, Silvia Barceló-Batllori, Martin R Larsen, Ethel Queralt
Background: Protein phosphatase 2A (PP2A) is a family of conserved serine/threonine phosphatases involved in several essential aspects of cell growth and proliferation. PP2ACdc55 phosphatase has been extensively related to cell cycle events in budding yeast, however few PP2ACdc55 substrates have been identified. Here, we performed a quantitative mass spectrometry approach to reveal new substrates of PP2ACdc55 phosphatase and new PP2A-related processes in mitotic arrested cells. Results: We identified 62 statistically significant PP2ACdc55 substrates involved mainly in actin-cytoskeleton organization...
April 24, 2018: GigaScience
https://www.readbyqxmd.com/read/29678583/identifying-the-sumo1-modification-of-fam122a-leading-to-the-degradation-of-pp2a-c%C3%AE-by-ubiquitin-proteasome-system
#20
Fangzhi Fan, Junxing Zhao, Yali Liu, Hongfang Zhao, Lietao Weng, Qingqing Li, Guoqiang Chen, Ying Xu
FAM122A is a highly conserved protein in mammals. Here, we identify that FAM122A can be sumoylated at lysine 89, which can be de-conjugated by SENP1. Furthermore, the sumoylation of FAM122A reduces the PP2A-Cα protein level together with the reduced phosphatase activity of PP2A, which suppresses cell proliferation. Collectively, our results suggest that the sumoylation of FAM122A may have a significant role in cellular function.
April 17, 2018: Biochemical and Biophysical Research Communications
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