scholarly journals Subunits B′γand B′ζof protein phosphatase 2A regulate photo-oxidative stress responses and growth inArabidopsis thaliana

2015 ◽  
Vol 38 (12) ◽  
pp. 2641-2651 ◽  
Author(s):  
Grzegorz Konert ◽  
Moona Rahikainen ◽  
Andrea Trotta ◽  
Guido Durian ◽  
Jarkko Salojärvi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Responses ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Phosphatase 2A ◽  
Oxidative Stress Responses

scholarly journals Oxidative Stress Induces Protein Phosphatase 2A-dependent Dephosphorylation of the Pocket Proteins pRb, p107, and p130

2003 ◽  
Vol 278 (21) ◽  
pp. 19509-19517 ◽  
Author(s):  
Lucia Cicchillitti ◽  
Pasquale Fasanaro ◽  
Paolo Biglioli ◽  
Maurizio C. Capogrossi ◽  
Fabio Martelli
Keyword(s):  
Oxidative Stress ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Pocket Proteins ◽  
Phosphatase 2A

scholarly journals Protein Phosphatase 2A Mediates Oxidative Stress Induced Apoptosis in Osteoblasts

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Chong-xin Huang ◽  
Bo Lv ◽  
Yue Wang
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Protein Phosphatase ◽  
Mammalian Cells ◽  
Protein Phosphatase 2A ◽  
Bone Diseases ◽  
Dna Lesions ◽  
Major Protein ◽  
Phosphatase 2A ◽  
Induced Apoptosis

Osteoporosis is one of the most common bone diseases, which is characterized by a systemic impairment of bone mass and fragility fractures. Age-related oxidative stress is highly associated with impaired osteoblastic dysfunctions and subsequent osteoporosis. In osteoblasts (bone formation cells), reactive oxygen species (ROS) are continuously generated and further cause lipid peroxidation, protein damage, and DNA lesions, leading to osteoblastic dysfunctions, dysdifferentiations, and apoptosis. Although much progress has been made, the mechanism responsible for oxidative stress induced cellular alternations and osteoblastic toxicity is still not fully elucidated. Here, we demonstrate that protein phosphatase 2A (PP2A), a major protein phosphatase in mammalian cells, mediates oxidative stress induced apoptosis in osteoblasts. Our results showed that lipid peroxidation products (4-HNE) may induce dramatic oxidative stress, inflammatory reactions, and apoptosis in osteoblasts. These oxidative stress responses may ectopically activate PP2A phosphatase activity, which may be mediated by inactivation of AKT/mTOR pathway. Moreover, inhibition of PP2A activity by okadaic acid might partly prevent osteoblastic apoptosis under oxidative conditions. These findings may reveal a novel mechanism to clarify the role of oxidative stress for osteoblastic apoptosis and provide new possibilities for the treatment of related bone diseases, such as osteoporosis.

scholarly journals Protein Phosphatase 2A Subunit PR70 Interacts with pRb and Mediates Its Dephosphorylation

2007 ◽  
Vol 28 (2) ◽  
pp. 873-882 ◽  
Author(s):  
Alessandra Magenta ◽  
Pasquale Fasanaro ◽  
Sveva Romani ◽  
Valeria Di Stefano ◽  
Maurizio C. Capogrossi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Phosphatase ◽  
Molecular Mechanisms ◽  
Protein Phosphatase 2A ◽  
Phosphate Removal ◽  
Regulatory Subunit ◽  
Phosphatase 2A ◽  
Retinoblastoma Tumor

ABSTRACT The retinoblastoma tumor suppressor protein (pRb) regulates cell proliferation and differentiation via phosphorylation-sensitive interactions with specific targets. While the role of cyclin/cyclin-dependent kinase complexes in the modulation of pRb phosphorylation has been extensively studied, relatively little is known about the molecular mechanisms regulating phosphate removal by phosphatases. Protein phosphatase 2A (PP2A) is constituted by a core dimer bearing catalytic activity and one variable B regulatory subunit conferring target specificity and subcellular localization. We previously demonstrated that PP2A core dimer binds pRb and dephosphorylates pRb upon oxidative stress. In the present study, we identified a specific PP2A-B subunit, PR70, that was associated with pRb both in vitro and in vivo. PR70 overexpression caused pRb dephosphorylation; conversely, PR70 knockdown prevented both pRb dephosphorylation and DNA synthesis inhibition induced by oxidative stress. Moreover, we found that intracellular Ca2+ mobilization was necessary and sufficient to trigger pRb dephosphorylation and PP2A phosphatase activity of PR70 was Ca2+ induced. These data underline the importance of PR70-Ca2+ interaction in the signal transduction mechanisms triggered by redox imbalance and leading to pRb dephosphorylation.

scholarly journals Potential Protein Phosphatase 2A Agents from Traditional Chinese Medicine against Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Kuan-Chung Chen ◽  
Hsin-Yi Chen ◽  
Calvin Yu-Chian Chen
Keyword(s):  
Stress Responses ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Human Tumor ◽  
Docking Simulation ◽  
Md Simulations ◽  
Tumor Promoter ◽  
Dynamic Conditions ◽  
Lead Compounds ◽  
Phosphatase 2A

Protein phosphatase 2A (PP2A) is an important phosphatase which regulates various cellular processes, such as protein synthesis, cell growth, cellular signaling, apoptosis, metabolism, and stress responses. It is a holoenzyme composed of the structural A and catalytic C subunits and a regulatory B subunit. As an environmental toxin, okadaic acid, is a tumor promoter and binds to PP2A catalytic C subunit and the cancer-associated mutations in PP2A structural A subunit in human tumor tissue; PP2A may have tumor-suppressing function. It is a potential drug target in the treatment of cancer. In this study, we screen the TCM compounds in TCM Database@Taiwan to investigate the potent lead compounds as PP2A agent. The results of docking simulation are optimized under dynamic conditions by MD simulations after virtual screening to validate the stability of H-bonds between PP2A-αprotein and each ligand. The top TCM candidates, trichosanatine and squamosamide, have potential binding affinities and interactions with key residues Arg89 and Arg214 in the docking simulation. In addition, these interactions were stable under dynamic conditions. Hence, we propose the TCM compounds, trichosanatine and squamosamide, as potential candidates as lead compounds for further study in drug development process with the PP2A-αprotein.

Protein phosphatase 2A-mediated cross-talk between p38 MAPK and ERK in apoptosis of cardiac myocytes

2004 ◽  
Vol 286 (6) ◽  
pp. H2204-H2212 ◽  
Author(s):  
Qinghang Liu ◽  
Polly A. Hofmann
Keyword(s):  
Oxidative Stress ◽  
P38 Mapk ◽  
Cross Talk ◽  
Protein Phosphatase ◽  
Ventricular Myocytes ◽  
Protein Phosphatase 2A ◽  
Erk Phosphorylation ◽  
Phosphatase 2A ◽  
Induced Apoptosis ◽  
Cardiac Ventricular Myocytes

Mitogen-activated protein kinases (MAPKs) play different regulatory roles in signaling oxidative stress-induced apoptosis in cardiac ventricular myocytes. The regulation and functional role of cross-talk between p38 MAPK and extracellular signal-regulated kinase (ERK) pathways were investigated in cardiac ventricular myocytes in the present study. We demonstrated that inhibition of p38 MAPK with SB-203580 and SB-239063 enhanced H2O2-stimulated ERK phosphorylation, whereas preactivation of p38 MAPK with sodium arsenite reduced H2O2-stimulated ERK phosphorylation. In addition, pretreatment of cells with the protein phosphatase 2A (PP2A) inhibitors okadaic acid and fostriecin increased basal and H2O2-stimulated ERK phosphorylation. We also found that PP2A coimmunoprecipitated with ERK and MAPK/ERK (MEK) in cardiac ventricular myocytes, and H2O2increased the ERK-associated PP2A activity that was blocked by inhibition of p38 MAPK. Finally, H2O2-induced apoptosis was attenuated by p38 MAPK or PP2A inhibition, whereas it was enhanced by MEK inhibition. Thus the present study demonstrated that p38 MAPK activation decreases H2O2-induced ERK activation through a PP2A-dependent mechanism in cardiac ventricular myocytes. This represents a novel cellular mechanism that allows for interaction of two opposing MAPK pathways and fine modulation of apoptosis during oxidative stress.

Oxidative stress induces inactivation of protein phosphatase 2A, promoting proinflammatory NF-κB in aged rat kidney

2013 ◽  
Vol 61 ◽  
pp. 206-217 ◽  
Author(s):  
Kyung Jin Jung ◽  
Dae Hyun Kim ◽  
Eun Kyeong Lee ◽  
Chang Woo Song ◽  
Byung Pal Yu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Phosphatase ◽  
Rat Kidney ◽  
Protein Phosphatase 2A ◽  
Aged Rat ◽  
Phosphatase 2A
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