PP2AC

Summary

Gene Symbol: PP2AC
Description: protein phosphatase 2 catalytic subunit alpha
Alias: PP2Ac, PP2CA, PP2Calpha, RP-C, serine/threonine-protein phosphatase 2A catalytic subunit alpha isoform, PP2A-alpha, protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform, protein phosphatase 2, catalytic subunit, alpha isozyme, replication protein C, serine/threonine protein phosphatase 2A, catalytic subunit, alpha isoform
Species: human
Products:     PP2AC

Top Publications

  1. Sunahori K, Juang Y, Tsokos G. Methylation status of CpG islands flanking a cAMP response element motif on the protein phosphatase 2Ac alpha promoter determines CREB binding and activity. J Immunol. 2009;182:1500-8 pubmed
    ..The catalytic subunit of the enzyme (PP2Ac), a part of the core enzyme, has two isoforms, alpha (PP2Ac alpha) and beta (PP2Ac beta), of which PP2Ac alpha is ..
  2. Sultan A, Nesslany F, Violet M, Bégard S, Loyens A, Talahari S, et al. Nuclear tau, a key player in neuronal DNA protection. J Biol Chem. 2011;286:4566-75 pubmed publisher
    ..These results highlight a novel role for nuclear Tau as a key player in early stress response. ..
  3. Sents W, Ivanova E, Lambrecht C, Haesen D, Janssens V. The biogenesis of active protein phosphatase 2A holoenzymes: a tightly regulated process creating phosphatase specificity. FEBS J. 2013;280:644-61 pubmed publisher
    ..Malfunctioning of these cellular control mechanisms contributes to human disease. The potential therapeutic benefits or pitfalls of interfering with these regulatory mechanisms will be briefly discussed. ..
  4. Du H, Wu K, Didoronkute A, Levy M, Todi N, Shchelokova A, et al. MID1 catalyzes the ubiquitination of protein phosphatase 2A and mutations within its Bbox1 domain disrupt polyubiquitination of alpha4 but not of PP2Ac. PLoS ONE. 2014;9:e107428 pubmed publisher
    ..Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced...
  5. Peterson R, Desai B, Hardwick J, Schreiber S. Protein phosphatase 2A interacts with the 70-kDa S6 kinase and is activated by inhibition of FKBP12-rapamycinassociated protein. Proc Natl Acad Sci U S A. 1999;96:4438-42 pubmed
  6. Ofek P, Ben Meir D, Kariv Inbal Z, Oren M, Lavi S. Cell cycle regulation and p53 activation by protein phosphatase 2C alpha. J Biol Chem. 2003;278:14299-305 pubmed
    ..The role of PP2C alpha in p53 activation is discussed. ..
  7. Kitajima T, Sakuno T, Ishiguro K, Iemura S, Natsume T, Kawashima S, et al. Shugoshin collaborates with protein phosphatase 2A to protect cohesin. Nature. 2006;441:46-52 pubmed
    ..Thus, we have revealed a conserved mechanism of centromeric protection of eukaryotic chromosomes in mitosis and meiosis. ..
  8. Tang Z, Shu H, Qi W, Mahmood N, Mumby M, Yu H. PP2A is required for centromeric localization of Sgo1 and proper chromosome segregation. Dev Cell. 2006;10:575-85 pubmed
    ..Our findings suggest that Bub1 targets PP2A to centromeres, which in turn maintains Sgo1 at centromeres by counteracting Plk1-mediated chromosome removal of Sgo1. ..
  9. Junttila M, Puustinen P, Niemelä M, Ahola R, Arnold H, Böttzauw T, et al. CIP2A inhibits PP2A in human malignancies. Cell. 2007;130:51-62 pubmed
    ..Thus, our data show that CIP2A is a human oncoprotein that inhibits PP2A and stabilizes c-Myc in human malignancies. ..

More Information

Publications211 found, 100 shown here

  1. Lammers T, Peschke P, Ehemann V, Debus J, Slobodin B, Lavi S, et al. Role of PP2Calpha in cell growth, in radio- and chemosensitivity, and in tumorigenicity. Mol Cancer. 2007;6:65 pubmed
    b>PP2Calpha is the representative member of the type 2C family of protein phosphatases, and it has recently been implicated in the regulation of p53-, TGFbeta-, cyclin-dependent kinase- and apoptosis-signaling...
  2. Aranda Orgilles B, Aigner J, Kunath M, Lurz R, Schneider R, Schweiger S. Active transport of the ubiquitin ligase MID1 along the microtubules is regulated by protein phosphatase 2A. PLoS ONE. 2008;3:e3507 pubmed publisher
    ..Furthermore, a failure in the microtubule directed transport of this protein complex would be an attractive mechanism underlying the pathogenesis of OS in patients with B-box1 mutations. ..
  3. LeNoue Newton M, Watkins G, Zou P, Germane K, McCorvey L, Wadzinski B, et al. The E3 ubiquitin ligase- and protein phosphatase 2A (PP2A)-binding domains of the Alpha4 protein are both required for Alpha4 to inhibit PP2A degradation. J Biol Chem. 2011;286:17665-71 pubmed publisher
    ..Alpha4 is one such regulatory protein that binds the PP2A catalytic subunit (PP2Ac) and protects it from polyubiquitination and degradation...
  4. Gergs U, Boknik P, Buchwalow I, Fabritz L, Matus M, Justus I, et al. Overexpression of the catalytic subunit of protein phosphatase 2A impairs cardiac function. J Biol Chem. 2004;279:40827-34 pubmed
    ..Taken together, these findings are indicative of the fundamental role of PP2A in cardiac function and imply that disturbances in protein phosphatases expression and activity may cause or aggravate the course of cardiac diseases. ..
  5. Krauss S, Griesche N, Jastrzebska E, Chen C, Rutschow D, Achmüller C, et al. Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1-PP2A protein complex. Nat Commun. 2013;4:1511 pubmed publisher
  6. McCright B, Rivers A, Audlin S, Virshup D. The B56 family of protein phosphatase 2A (PP2A) regulatory subunits encodes differentiation-induced phosphoproteins that target PP2A to both nucleus and cytoplasm. J Biol Chem. 1996;271:22081-9 pubmed
    ..These studies demonstrate an increasing diversity of regulatory mechanisms to control the activity of this key intracellular protein phosphatase and suggest distinct functions for isoforms targeted to different intracellular locations. ..
  7. Cheng A, Kaldis P, Solomon M. Dephosphorylation of human cyclin-dependent kinases by protein phosphatase type 2C alpha and beta 2 isoforms. J Biol Chem. 2000;275:34744-9 pubmed
  8. Luss H, Klein Wiele O, Boknik P, Herzig S, Knapp J, Linck B, et al. Regional expression of protein phosphatase type 1 and 2A catalytic subunit isoforms in the human heart. J Mol Cell Cardiol. 2000;32:2349-59 pubmed
    ..Thus, lower protein expression of PP2A in atrium could contribute to the faster relaxation by increasing the phosphorylation state of TnI. We conclude that expression of PP1 and PP2A isoforms is regionally regulated in the human heart. ..
  9. McConnell J, Watkins G, Soss S, Franz H, McCorvey L, Spiller B, et al. Alpha4 is a ubiquitin-binding protein that regulates protein serine/threonine phosphatase 2A ubiquitination. Biochemistry. 2010;49:1713-8 pubmed publisher
    ..regulatory mechanisms control the activity of the protein serine/threonine phosphatase 2A catalytic subunit (PP2Ac), including post-translational modifications and its association with regulatory subunits and interacting proteins...
  10. Liu J, Prickett T, Elliott E, Meroni G, Brautigan D. Phosphorylation and microtubule association of the Opitz syndrome protein mid-1 is regulated by protein phosphatase 2A via binding to the regulatory subunit alpha 4. Proc Natl Acad Sci U S A. 2001;98:6650-5 pubmed
    ..Human birth defects may result from environmental or genetic disruption of this regulatory cycle. ..
  11. Wong L, Chang C, Koay E, Zhang D. Tyrosine phosphorylation of PP2A is regulated by HER-2 signalling and correlates with breast cancer progression. Int J Oncol. 2009;34:1291-301 pubmed
    ..Our data provide meaningful information in the elucidation of the HER-2-driven tyrosine phosphorylation network, and in the development of phosphopeptide-related targets as prognostication indicators. ..
  12. Watkins G, Wang N, Mazalouskas M, Gomez R, Guthrie C, Kraemer B, et al. Monoubiquitination promotes calpain cleavage of the protein phosphatase 2A (PP2A) regulatory subunit ?4, altering PP2A stability and microtubule-associated protein phosphorylation. J Biol Chem. 2012;287:24207-15 pubmed publisher
    ..4 binds the PP2A catalytic subunit (PP2Ac) and the microtubule-associated E3 ubiquitin ligase MID1, and through unknown mechanisms can both reduce and ..
  13. Tehrani M, Mumby M, Kamibayashi C. Identification of a novel protein phosphatase 2A regulatory subunit highly expressed in muscle. J Biol Chem. 1996;271:5164-70 pubmed
    ..The nuclear localization of expressed B'alpha suggests that some variants of the B' subunit are involved in the nuclear functions of PP2A. ..
  14. Zolnierowicz S. Type 2A protein phosphatase, the complex regulator of numerous signaling pathways. Biochem Pharmacol. 2000;60:1225-35 pubmed
    ..Common to all forms of PP2A is a catalytic subunit (PP2Ac) which can form two distinct complexes, one with a structural subunit termed PR65/A and another with an alpha4 ..
  15. Kong M, Ditsworth D, Lindsten T, Thompson C. Alpha4 is an essential regulator of PP2A phosphatase activity. Mol Cell. 2009;36:51-60 pubmed publisher
    ..These findings demonstrate that alpha4 plays a required role in regulating the assembly and maintenance of adaptive PP2A phosphatase complexes. ..
  16. McDonald W, Thomas L, Koirala S, Too C. Progestin-inducible EDD E3 ubiquitin ligase binds to α4 phosphoprotein to regulate ubiquitination and degradation of protein phosphatase PP2Ac. Mol Cell Endocrinol. 2014;382:254-261 pubmed publisher
    Mammalian α4 phosphoprotein binds to the protein phosphatase 2A catalytic subunit (PP2Ac) to regulate PP2A activity, and to poly(A)-binding protein (PABP) and progestin-inducible EDD E3 ubiquitin ligase...
  17. Ahn C, Ahn H, Pai H. Overexpression of the PP2A regulatory subunit Tap46 leads to enhanced plant growth through stimulation of the TOR signalling pathway. J Exp Bot. 2015;66:827-40 pubmed publisher
    ..These findings suggest that Tap46 modulates plant growth as a positive effector of the TOR signalling pathway and Tap46/PP2Ac protein abundance is regulated by TOR activity.
  18. Arrouss I, Decaudin D, Choquet S, Azar N, Parizot C, Zini J, et al. Cell penetrating peptides as a therapeutic strategy in chronic lymphocytic leukemia. Protein Pept Lett. 2015;22:539-46 pubmed
    ..Our results strongly suggest that DPT-C9h peptide has tumour specificity and that caspase-9/PP2Ac interaction constitutes a novel therapeutic approach for the treatment in CLL patients.
  19. Li H, Cai X, Shouse G, Piluso L, Liu X. A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. EMBO J. 2007;26:402-11 pubmed
    ..These results suggest a molecular mechanism for B56gamma-mediated tumor suppression and provide a potential route for regulation of B56gamma-specific PP2A complex function. ..
  20. Lucas C, Harris R, Holcroft A, Scott L, Carmell N, McDonald E, et al. Second generation tyrosine kinase inhibitors prevent disease progression in high-risk (high CIP2A) chronic myeloid leukaemia patients. Leukemia. 2015;29:1514-23 pubmed publisher
    ..The data supports the view that CIP2A inhibits PP2Ac, stabilising E2F1, creating a CIP2A/c-Myc/E2F1 positive feedback loop, which imatinib cannot overcome.
  21. Gong F, Wu M, Shen M, Zhi Q, Xu Z, Wang R, et al. PP2A inhibitors arrest G2/M transition through JNK/Sp1- dependent down-regulation of CDK1 and autophagy-dependent up-regulation of p21. Oncotarget. 2015;6:18469-83 pubmed
    ..whether these expression changes were executed in a PP2A-dependent manner, we targeted the PP2A catalytic subunit (PP2Ac) using siRNA and evaluated gene expression with a microarray...
  22. Shouse G, De Necochea Campion R, Mirshahidi S, Liu X, Chen C. Novel B55α-PP2A mutations in AML promote AKT T308 phosphorylation and sensitivity to AKT inhibitor-induced growth arrest. Oncotarget. 2016;7:61081-61092 pubmed publisher
    ..Together our data illustrate the importance of the B55α-PP2A-AKT pathway in leukemogenesis. Screening for disruptions in this pathway at initial AML diagnosis may predict response to targeted therapies against AKT and PP2A. ..
  23. Lashine Y, Salah S, Aboelenein H, Abdelaziz A. Correcting the expression of miRNA-155 represses PP2Ac and enhances the release of IL-2 in PBMCs of juvenile SLE patients. Lupus. 2015;24:240-7 pubmed publisher
    ..The mRNA of the catalytic subunit of PP2A (PP2Ac) showed significant upregulation in PBMCs from SLE and FMF but not in JIA patients...
  24. Wong P, Feng Y, Wang J, Shi R, Jiang X. Regulation of autophagy by coordinated action of mTORC1 and protein phosphatase 2A. Nat Commun. 2015;6:8048 pubmed publisher
    ..Taken together, concurrent mTORC1 inactivation and PP2A-B55α stimulation fuel ULK1-dependent autophagy. ..
  25. Gutiérrez Monreal M, Villela L, Baltazar S, Perfecto Avalos Y, Cardineau G, Scott S. A PER3 polymorphism is associated with better overall survival in diffuse large B-cell lymphoma in Mexican population. Cancer Biomark. 2015;15:699-705 pubmed publisher
    ..001) also showed differences in overall survival. No clinical differences were observed in mutated vs. non-mutated patients. This work suggests a role of PER3 rs10462020 in predicting a prognosis in DLBCL overall survival of patients. ..
  26. Shern J, Sharer J, Pallas D, Bartolini F, Cowan N, Reed M, et al. Cytosolic Arl2 is complexed with cofactor D and protein phosphatase 2A. J Biol Chem. 2003;278:40829-36 pubmed
    ..Our data suggest functional roles for the cytosolic Arl2 complex in modulating tubulin and microtubule behavior as well as a possible role in apoptosis. ..
  27. Chun Y. Knockdown of clusterin expression increases the in vitro sensitivity of human prostate cancer cells to paclitaxel. J Toxicol Environ Health A. 2014;77:1443-50 pubmed publisher
    ..in a decrease in protein expression of phospho-Akt and an increase in expression of proteins phosphatase type 2AC (PP2AC) and phosphorylation of p38. However, treatment with PP2AC siRNA exerted minimal effects on clusterin expression...
  28. Sato T, Shiba Ishii A, Kim Y, Dai T, Husni R, Hong J, et al. miR-3941: A novel microRNA that controls IGBP1 expression and is associated with malignant progression of lung adenocarcinoma. Cancer Sci. 2017;108:536-542 pubmed publisher
    ..1 (IGBP1) is universally overexpressed in lung adenocarcinoma and exerts an anti-apoptotic effect by binding to PP2Ac. However, the molecular mechanism of IGBP1 overexpression is still unclear...
  29. Eleftheriadou O, Boguslavskyi A, Longman M, Cowan J, Francois A, Heads R, et al. Expression and regulation of type 2A protein phosphatases and alpha4 signalling in cardiac health and hypertrophy. Basic Res Cardiol. 2017;112:37 pubmed publisher
    ..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 ..
  30. Carrey E, Campbell D, Hardie D. Phosphorylation and activation of hamster carbamyl phosphate synthetase II by cAMP-dependent protein kinase. A novel mechanism for regulation of pyrimidine nucleotide biosynthesis. EMBO J. 1985;4:3735-42 pubmed
    ..The physiological role of this phosphorylation in the stimulation of cell proliferation by growth factors and other mitogens is discussed. ..
  31. Ikeda S, Kishida M, Matsuura Y, Usui H, Kikuchi A. GSK-3beta-dependent phosphorylation of adenomatous polyposis coli gene product can be modulated by beta-catenin and protein phosphatase 2A complexed with Axin. Oncogene. 2000;19:537-45 pubmed
    ..Taken together, these results suggest that GSK-3beta-dependent phosphorylation of APC can be modulated by beta-catenin and PP2A complexed with Axin. ..
  32. Lechward K, Sugajska E, De Baere I, Goris J, Hemmings B, Zolnierowicz S. Interaction of nucleoredoxin with protein phosphatase 2A. FEBS Lett. 2006;580:3631-7 pubmed
    A trimeric protein phosphatase 2A (PP2A(T55)) composed of the catalytic (PP2Ac), structural (PR65/A), and regulatory (PR55/B) subunits was isolated from rabbit skeletal muscle by thiophosphorylase affinity chromatography, and contained ..
  33. Hoffmeister M, Prelle C, Küchler P, Kovacevic I, Moser M, Müller Esterl W, et al. The ubiquitin E3 ligase NOSIP modulates protein phosphatase 2A activity in craniofacial development. PLoS ONE. 2014;9:e116150 pubmed publisher
    ..We conclude, that NOSIP is a critical modulator of brain and craniofacial development in mice and a candidate gene for holoprosencephaly in humans. ..
  34. Zhang Y, Wang X, Qin X, Wang X, Liu F, White E, et al. PP2AC Level Determines Differential Programming of p38-TSC-mTOR Signaling and Therapeutic Response to p38-Targeted Therapy in Colorectal Cancer. EBioMedicine. 2015;2:1944-56 pubmed publisher
    ..We further show that PP2AC is differentially expressed in the two different CRC subgroups, which determines the programing of p38-TSC-mTORC1 ..
  35. Strovel E, Wu D, Sussman D. Protein phosphatase 2Calpha dephosphorylates axin and activates LEF-1-dependent transcription. J Biol Chem. 2000;275:2399-403 pubmed
    ..PP2C utilizes Axin as a substrate both in vitro and in vivo and decreases its half-life. These results indicate that PP2C is a positive regulator of Wnt signal transduction and mediates its effects through the dephosphorylation of Axin. ..
  36. Bhardwaj A, Singh S, Srivastava S, Honkanen R, Reed E, Singh A. Modulation of protein phosphatase 2A activity alters androgen-independent growth of prostate cancer cells: therapeutic implications. Mol Cancer Ther. 2011;10:720-31 pubmed publisher
    ..Altogether, our findings suggest that modulation of PP2A activity may represent an alternative therapeutic approach for the treatment of advanced androgen-independent prostate cancer. ..
  37. Sunahori K, Nagpal K, Hedrich C, Mizui M, Fitzgerald L, Tsokos G. The catalytic subunit of protein phosphatase 2A (PP2Ac) promotes DNA hypomethylation by suppressing the phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/phosphorylated ERK/DNMT1 protein pathway . J Biol Chem. 2013;288:21936-44 pubmed publisher
    ..Here, we investigated whether the catalytic subunit of protein phosphatase 2A (PP2Ac), which is overexpressed in SLE T-cells, contributes to reduced DNA methylation...
  38. Li W, Wang L, Sheng X, Yan C, Zhou R, Hang J, et al. Molecular basis for the selective and ABA-independent inhibition of PP2CA by PYL13. Cell Res. 2013;23:1369-79 pubmed publisher
    ..Here, we show that PYL13 selectively inhibits the phosphatase activity of PP2CA independent of ABA. The crystal structure of PYL13-PP2CA complex, which was determined at 2...
  39. Shimoyama S, Kasai S, Kahn Perlès B, Kikuchi H. Dephosphorylation of Sp1 at Ser-59 by protein phosphatase 2A (PP2A) is required for induction of CYP1A1 transcription after treatment with 2,3,7,8-tetrachlorodibenzo-p-dioxin or omeprazole. Biochim Biophys Acta. 2014;1839:107-15 pubmed publisher
    ..These results indicate that the signals from TCDD or OP caused PP2A-mediated dephosphorylation of Sp1 at Ser-59 and induced CYP1A1 transcription. This signaling pathway was independent of the AhR-mediated pathway. ..
  40. Wang Y, Liu J, Chen M, Du T, Duan C, Gao G, et al. The novel mechanism of rotenone-induced α-synuclein phosphorylation via reduced protein phosphatase 2A activity. Int J Biochem Cell Biol. 2016;75:34-44 pubmed publisher
    ..inhibition of PP2A activity by increased phosphorylation of tyrosine 307 at the catalytic subunit of PP2A (pTyr307 PP2Ac)...
  41. Ma J, Arnold H, Lilly M, Sears R, Kraft A. Negative regulation of Pim-1 protein kinase levels by the B56beta subunit of PP2A. Oncogene. 2007;26:5145-53 pubmed
    ..On the basis of these observations, we hypothesize that phosphorylated Pim-1 binds Pin1 allowing the interaction of PP2A through B56beta. Dephosphorylation of Pim-1 then allows for ubiquitinylation and protein degradation of Pim-1. ..
  42. Preuss K, Pfreundschuh M, Fadle N, Regitz E, Raudies S, Murwaski N, et al. Hyperphosphorylation of autoantigenic targets of paraproteins is due to inactivation of PP2A. Blood. 2011;118:3340-6 pubmed publisher
  43. Yabe R, Miura A, Usui T, Mudrak I, Ogris E, Ohama T, et al. Protein Phosphatase Methyl-Esterase PME-1 Protects Protein Phosphatase 2A from Ubiquitin/Proteasome Degradation. PLoS ONE. 2015;10:e0145226 pubmed publisher
    ..PME-1) catalyzes specifically the demethylation of the C-terminal Leu309 residue of PP2A catalytic subunit (PP2Ac)...
  44. Chen J, Yu F, Liu Y, Du C, Li X, Zhu S, et al. FERONIA interacts with ABI2-type phosphatases to facilitate signaling cross-talk between abscisic acid and RALF peptide in Arabidopsis. Proc Natl Acad Sci U S A. 2016;113:E5519-27 pubmed publisher
    ..RESISTANCE (PYR)/PYR1-LIKE (PYL)/REGULATORY COMPONENTS OF ABA RECEPTORS (RCAR)-A-type protein phosphatase type 2C (PP2CA) modules...
  45. Park J, Leong M, Buse P, Maiyar A, Firestone G, Hemmings B. Serum and glucocorticoid-inducible kinase (SGK) is a target of the PI 3-kinase-stimulated signaling pathway. EMBO J. 1999;18:3024-33 pubmed
    ..Both hyperphosphorylation and nuclear translocation could be inhibited by wortmannin, but not by rapamycin. ..
  46. Ruvolo P, Clark W, Mumby M, Gao F, May W. A functional role for the B56 alpha-subunit of protein phosphatase 2A in ceramide-mediated regulation of Bcl2 phosphorylation status and function. J Biol Chem. 2002;277:22847-52 pubmed
    ..These findings suggest a role for B56 alpha in regulating the Bcl2 phosphatase. ..
  47. Godet A, Guergnon J, Galioot A, Falanga P, Colle J, Cayla X, et al. [Targeting of PP2A enzymes by viral proteins and cancer signalling]. Med Sci (Paris). 2011;27:1106-11 pubmed publisher
    ..The impact of such PP2A targeting for biomedical search, and in further therapeutic developments against cancer, will also be discussed. ..
  48. Miyakawa K, Sawasaki T, Matsunaga S, Tokarev A, Quinn G, Kimura H, et al. Interferon-induced SCYL2 limits release of HIV-1 by triggering PP2A-mediated dephosphorylation of the viral protein Vpu. Sci Signal. 2012;5:ra73 pubmed publisher
    ..Together, these results suggest that SCYL2 serves as a regulatory factor for Vpu, reducing the extent of Vpu phosphorylation and consequently enhancing BST2-mediated viral restriction. ..
  49. Tan X, Chen M. MYLK and MYL9 expression in non-small cell lung cancer identified by bioinformatics analysis of public expression data. Tumour Biol. 2014;35:12189-200 pubmed publisher
    ..These genes may be also relevant to NSCLC metastasis. Future investigations with large sample sizes needed to verify these findings. ..
  50. Wang Y, He H, Liu Z, Cao Z, Wang X, Yang K, et al. Effects of TNF-α on Cementoblast Differentiation, Mineralization, and Apoptosis. J Dent Res. 2015;94:1225-32 pubmed publisher
    ..Various signaling pathways, such as p53, PP2AC, p38, Erk1/2, JNK, PI3K-Akt, and NF-κB, were activated during this process...
  51. Zhao L, Li R, Gan Y. Knockdown of Yin Yang 1 enhances anticancer effects of cisplatin through protein phosphatase 2A-mediated T308 dephosphorylation of AKT. Cell Death Dis. 2018;9:747 pubmed publisher
  52. Kolupaeva V, Janssens V. PP1 and PP2A phosphatases--cooperating partners in modulating retinoblastoma protein activation. FEBS J. 2013;280:627-43 pubmed publisher
  53. Rahman A, Khan K, Al Khaledi G, Khan I, Al Shemary T. Over activation of hippocampal serine/threonine protein phosphatases PP1 and PP2A is involved in lead-induced deficits in learning and memory in young rats. Neurotoxicology. 2012;33:370-83 pubmed publisher
    ..These findings suggest the overactivation of PP1 and PP2A, together with changes in tau phosphorylation, as a potential mechanism of lead-induced deficits in learning and memory. ..
  54. Li J, Sheng C, Li W, Zheng J. Protein phosphatase-2A is down-regulated in patients within clear cell renal cell carcinoma. Int J Clin Exp Pathol. 2014;7:1147-53 pubmed
    ..Further studies on the cellular functions of PP2A need to address these issues. ..
  55. Muñiz García M, Muro M, Mazzocchi L, País S, Stritzler M, Schlesinger M, et al. The protein phosphatase 2A catalytic subunit StPP2Ac2b acts as a positive regulator of tuberization induction in Solanum tuberosum L. Plant Mol Biol. 2017;93:227-245 pubmed publisher
    ..In cultivated potato (Solanum tuberosum), six PP2A catalytic subunits (StPP2Ac) were identified. The PP2Ac of the subfamily I (StPP2Ac1, 2a and 2b) were suggested to be involved in the tuberization signaling in leaves, ..
  56. Ni L, Yang C, Gioeli D, Frierson H, Toft D, Paschal B. FKBP51 promotes assembly of the Hsp90 chaperone complex and regulates androgen receptor signaling in prostate cancer cells. Mol Cell Biol. 2010;30:1243-53 pubmed publisher
    ..Because the superchaperone complex plays a critical role in determining the ligand-binding competence and transcription function of AR, it provides an attractive target for inhibiting AR activity in prostate cancer cells. ..
  57. Xi P, Zhou L, Wang M, Liu J, Cong Y. Serine/threonine-protein phosphatase 2A physically interacts with human telomerase reverse transcriptase hTERT and regulates its subcellular distribution. J Cell Biochem. 2013;114:409-17 pubmed publisher
    ..We showed that both PP2A catalytic subunit PP2AC and scaffolding subunit PR65 interacted with hTERT in vivo and in vitro and inhibited telomerase activity...
  58. Lee C, Yang F, Chang H, Chou H, Tan B, Lee S. Interaction between salt-inducible kinase 2 and protein phosphatase 2A regulates the activity of calcium/calmodulin-dependent protein kinase I and protein phosphatase methylesterase-1. J Biol Chem. 2014;289:21108-19 pubmed
    ..Furthermore, this study suggests that the tightly linked regulatory loop comprised of the SIK2-PP2A and CaMKI and PME-1 networks may function in fine-tuning cell proliferation and stress response. ..
  59. Fielhaber J, Han Y, Tan J, Xing S, Biggs C, Joung K, et al. Inactivation of mammalian target of rapamycin increases STAT1 nuclear content and transcriptional activity in alpha4- and protein phosphatase 2A-dependent fashion. J Biol Chem. 2009;284:24341-53 pubmed publisher
    ..complex composed of mTOR, STAT1, the Tap42 homologue alpha4, and the protein phosphatase 2A catalytic subunit (PP2Ac)...
  60. Antony R, Lukiw W, Bazan N. Neuroprotectin D1 induces dephosphorylation of Bcl-xL in a PP2A-dependent manner during oxidative stress and promotes retinal pigment epithelial cell survival. J Biol Chem. 2010;285:18301-8 pubmed publisher
    ..Thus, NPD1 modulates the activation of this Bcl-2 family protein by dephosphorylating in a PP2A-dependent manner, suggesting a coordinated, NPD1-mediated regulation of cell survival in response to oxidative stress. ..
  61. Liang D, Zeng Q, Xu Z, Zhang H, Gui L, Xu C, et al. BAFF activates Erk1/2 promoting cell proliferation and survival by Ca2+-CaMKII-dependent inhibition of PP2A in normal and neoplastic B-lymphoid cells. Biochem Pharmacol. 2014;87:332-43 pubmed publisher
    ..Our data suggest that inhibitors of CaMKII and Erk1/2, activator of PP2A or manipulation of intracellular Ca(2+) may be exploited for prevention of excessive BAFF-induced aggressive B-cell malignancies and autoimmune diseases. ..
  62. Xian L, Hou S, Huang Z, Tang A, Shi P, Wang Q, et al. Liver-specific deletion of Ppp2cα enhances glucose metabolism and insulin sensitivity. Aging (Albany NY). 2015;7:223-32 pubmed
    ..Previous study showed that, in the liver, the catalytic subunit of PP2A (PP2Ac) is closely associated with insulin resistance syndrome, which is characterized by glucose intolerance and ..
  63. Okada M, Ohtake F, Nishikawa H, Wu W, Saeki Y, Takana K, et al. Liganded ERα Stimulates the E3 Ubiquitin Ligase Activity of UBE3C to Facilitate Cell Proliferation. Mol Endocrinol. 2015;29:1646-57 pubmed publisher
    ..The mitotic role of estrogen may contribute to its effects on proliferation in addition to its roles in target gene expression. ..
  64. Adams D, Coffee R, Zhang H, Pelech S, Strack S, Wadzinski B. Positive regulation of Raf1-MEK1/2-ERK1/2 signaling by protein serine/threonine phosphatase 2A holoenzymes. J Biol Chem. 2005;280:42644-54 pubmed
    ..Together these findings indicate that PP2A ABalphaC and ABdeltaC holoenzymes function as positive regulators of Raf1-MEK1/2-ERK1/2 signaling by targeting Raf1. ..
  65. Takemoto A, Maeshima K, Ikehara T, Yamaguchi K, Murayama A, Imamura S, et al. The chromosomal association of condensin II is regulated by a noncatalytic function of PP2A. Nat Struct Mol Biol. 2009;16:1302-8 pubmed publisher
    ..Additionally, we found that the chromokinesin KIF4a is also targeted to chromosomes via the noncatalytic activity of PP2A. Thus, our studies reveal a previously unknown contribution of PP2A to chromosome assembly. ..
  66. Wang J, Liu X. [Action of protein phosphatase-1 on Tat-dependent HIV-1 transcription and its related inhibitors]. Yao Xue Xue Bao. 2009;44:1343-7 pubmed
    ..In this review, we discuss the action of PP1 in Tat-induced HIV-1 transcription and related to PP1 inhibitors. ..
  67. Yakovlev V. Nitric oxide-dependent downregulation of BRCA1 expression promotes genetic instability. Cancer Res. 2013;73:706-15 pubmed publisher
    ..In summary, NO/RNS stimulates genetic instability by inhibiting BRCA1 expression and shifting DNA repair from high fidelity to error-prone mechanisms. ..
  68. Yu X, Teng X, Wang F, Zheng Y, Qu G, Zhou Y, et al. Metabolic control of regulatory T cell stability and function by TRAF3IP3 at the lysosome. J Exp Med. 2018;215:2463-2476 pubmed publisher
    ..TRAF3IP3 restricts mTORC1 signaling by recruiting the serine-threonine phosphatase catalytic subunit (PP2Ac) to the lysosome, thereby facilitating the interaction of PP2Ac with the mTORC1 component Raptor...
  69. Chung H, Nairn A, Murata K, Brautigan D. Mutation of Tyr307 and Leu309 in the protein phosphatase 2A catalytic subunit favors association with the alpha 4 subunit which promotes dephosphorylation of elongation factor-2. Biochemistry. 1999;38:10371-6 pubmed
    ..Signals that affect phosphorylation or methylation of the C subunit of PP2A may promote subunit exchange and direct phosphatase activity to specific intracellular substrates. ..
  70. ten Klooster J, Leeuwen I, Scheres N, Anthony E, Hordijk P. Rac1-induced cell migration requires membrane recruitment of the nuclear oncogene SET. EMBO J. 2007;26:336-45 pubmed
    ..Our results suggest a model in which Rac1-stimulated cell motility requires both effector loop-based downstream signalling and recruitment of a signalling amplifier, that is, SET, through the hypervariable C-terminus. ..
  71. Scheidtmann K, Virshup D, Kelly T. Protein phosphatase 2A dephosphorylates simian virus 40 large T antigen specifically at residues involved in regulation of DNA-binding activity. J Virol. 1991;65:2098-101 pubmed
    ..Increasing amounts of phosphatase sequentially removed the phosphates from serine residues 120, 123, 677, and perhaps 679, residues which have been implicated in regulating the DNA-binding activity of LT. ..
  72. Bharucha D, Zhou M, Nekhai S, Brady J, Shukla R, Kumar A. A protein phosphatase from human T cells augments tat transactivation of the human immunodeficiency virus type 1 long-terminal repeat. Virology. 2002;296:6-16 pubmed
    ..The results suggest a unique role of the Tat-associated phosphatase which regulates viral transcription by target-specific dephosphorylation of RNAPII during the early stages of elongation. ..
  73. Xiao L, Gong L, Yuan D, Deng M, Zeng X, Chen L, et al. Protein phosphatase-1 regulates Akt1 signal transduction pathway to control gene expression, cell survival and differentiation. Cell Death Differ. 2010;17:1448-62 pubmed publisher
    ..These results show that PP-1 acts as a major phosphatase to dephosphorylate AKT at Thr-450 and thus modulate its functions. ..
  74. Kawano S, Maruyama J, Nagashima S, Inami K, Qiu W, Iwasa H, et al. A cell-based screening for TAZ activators identifies ethacridine, a widely used antiseptic and abortifacient, as a compound that promotes dephosphorylation of TAZ and inhibits adipogenesis in C3H10T1/2 cells. J Biochem. 2015;158:413-23 pubmed publisher
    ..Ethacridine inhibits adipogenesis in mesenchymal C3H10T1/2 cells through the activation of TAZ. This finding suggests that ethacridine is a bona fide TAZ activator and supports that our assay is useful to discover TAZ activators. ..
  75. Hu X, Garcia C, Fazli L, Gleave M, Vitek M, Jansen M, et al. Inhibition of Pten deficient Castration Resistant Prostate Cancer by Targeting of the SET - PP2A Signaling axis. Sci Rep. 2015;5:15182 pubmed publisher
    ..Collectively, our data supports a critical role for the SET-PP2A signaling axis in CRPC progression and hormone resistant disease. ..
  76. Ríos J, Godoy J, Inestrosa N. Wnt3a ligand facilitates autophagy in hippocampal neurons by modulating a novel GSK-3β-AMPK axis. Cell Commun Signal. 2018;16:15 pubmed publisher
    ..GSK-3β inhibition, AMPK activation, PP2Ac expression, and LC3 processing were examined by western blotting...
  77. Li L, Ren C, Tahir S, Ren C, Thompson T. Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A. Mol Cell Biol. 2003;23:9389-404 pubmed
    ..Our studies therefore reveal a novel mechanism of Akt activation in prostate cancer and potentially other malignancies. ..
  78. Pan C, Tang J, Xu Y, Xiao P, Liu H, Wang H, et al. The catalytic role of the M2 metal ion in PP2Cα. Sci Rep. 2015;5:8560 pubmed publisher
  79. Vázquez Carballo A, Ceperuelo Mallafré V, Chacon M, Maymó Masip E, Lorenzo M, Porras A, et al. TWEAK prevents TNF-?-induced insulin resistance through PP2A activation in human adipocytes. Am J Physiol Endocrinol Metab. 2013;305:E101-12 pubmed publisher
    ..Overall, our data reveal a protective role of TWEAK in glucose homeostasis and identify PP2A as a new driver in the modulation of TNF-? signaling by sTWEAK. ..
  80. Calais J, Ojopi E, Morya E, Sameshima K, Ribeiro S. Experience-dependent upregulation of multiple plasticity factors in the hippocampus during early REM sleep. Neurobiol Learn Mem. 2015;122:19-27 pubmed publisher
    ..The experience-dependent induction of multiple plasticity-related genes in the hippocampus during early REM adds experimental support to the synaptic embossing theory. ..
  81. Li Z, Waadt R, Schroeder J. Release of GTP Exchange Factor Mediated Down-Regulation of Abscisic Acid Signal Transduction through ABA-Induced Rapid Degradation of RopGEFs. PLoS Biol. 2016;14:e1002461 pubmed publisher
    ..Interestingly, RopGEF1 undergoes constitutive degradation in pp2c quadruple abi1/abi2/hab1/pp2ca mutant plants, revealing that active PP2C protein phosphatases protect and stabilize RopGEF1 from ABA-mediated ..
  82. Lee S, Lee Y, Choi J, Yoon M, Han J. Phosphatidic acid induces decidualization by stimulating Akt-PP2A binding in human endometrial stromal cells. FEBS J. 2016;283:4163-4175 pubmed publisher
    ..Consistent with this observation, treatment with okadaic acid, a PP2A inhibitor, also inhibited cAMP-induced decidualization by blocking Akt dephosphorylation. ..
  83. Zhang Y, Zhang J, Wang E, Qian W, Fan Y, Feng Y, et al. Microcystin-Leucine-Arginine Induces Tau Pathology Through Bα Degradation via Protein Phosphatase 2A Demethylation and Associated Glycogen Synthase Kinase-3β Phosphorylation. Toxicol Sci. 2018;162:475-487 pubmed publisher
    ..The present study investigated the role of PP2A catalytic subunit (PP2Ac) demethylation and its link with glycogen synthase kinase-3β (GSK)-3β in tau hyperphosphorylation induced by MC-..
  84. Lowe M, Gonatas N, Warren G. The mitotic phosphorylation cycle of the cis-Golgi matrix protein GM130. J Cell Biol. 2000;149:341-56 pubmed
    ..The active species was identified as heterotrimeric phosphatase containing the Balpha regulatory subunit, suggesting a role for this isoform in the reassembly of mitotic Golgi membranes at the end of mitosis. ..
  85. Dozier C, Bonyadi M, Baricault L, Tonasso L, Darbon J. Regulation of Chk2 phosphorylation by interaction with protein phosphatase 2A via its B' regulatory subunit. Biol Cell. 2004;96:509-17 pubmed
    ..Finally, we demonstrated that overexpressing B'gamma3 in HEK293 suppressed the phosphorylation of Chk2 induced by a genotoxic treatment, suggesting that PP2A may counteract the action of the checkpoint kinase in living cells. ..
  86. Kray A, Carter R, Pennington K, Gomez R, Sanders L, Llanes J, et al. Positive regulation of IkappaB kinase signaling by protein serine/threonine phosphatase 2A. J Biol Chem. 2005;280:35974-82 pubmed
    ..Taken together, these data provide strong evidence that the formation of IKK.PP2A complexes is required for the proper induction of IkappaB kinase activity in vivo. ..
  87. Chen J, Hu R, Zhu Y, Shen G, Zhang H. Arabidopsis PHOSPHOTYROSYL PHOSPHATASE ACTIVATOR is essential for PROTEIN PHOSPHATASE 2A holoenzyme assembly and plays important roles in hormone signaling, salt stress response, and plant development. Plant Physiol. 2014;166:1519-34 pubmed publisher
    ..In particular, AtPTPA deficiency leads to decreased methylation in PP2A-C subunits (PP2Ac)...
  88. Hua G, Xiaolei L, Weiwei Y, Hao W, Yuangang Z, Dongmei L, et al. Protein phosphatase 2A is involved in the tyrosine hydroxylase phosphorylation regulated by α-synuclein. Neurochem Res. 2015;40:428-37 pubmed publisher
    ..Thus our findings may provide an insight into the complicated pathogenesis of PD as well as some clues to the development of novel therapeutic strategies targeting at PP2A. ..
  89. Liu F, Zaidi T, Iqbal K, Grundke Iqbal I, Gong C. Aberrant glycosylation modulates phosphorylation of tau by protein kinase A and dephosphorylation of tau by protein phosphatase 2A and 5. Neuroscience. 2002;115:829-37 pubmed
    ..The combined impact of this modulation may be to make tau more susceptible to becoming abnormally hyperphosphorylated. ..
  90. Cheng A, Gerry S, Kaldis P, Solomon M. Biochemical characterization of Cdk2-Speedy/Ringo A2. BMC Biochem. 2005;6:19 pubmed
  91. Chan P, Lim L, Manser E. PAK is regulated by PI3K, PIX, CDC42, and PP2Calpha and mediates focal adhesion turnover in the hyperosmotic stress-induced p38 pathway. J Biol Chem. 2008;283:24949-61 pubmed publisher
    Fractionation of brain extracts and functional biochemical assays identified PP2Calpha, a serine/threonine phosphatase, as the major biochemical activity inhibiting PAK1...
  92. Xu X, Ouyang J, Xie P, Chen J. [Changes of activity and expression of protein phosphatase type 2A during the apoptosis of NB4 and MR2 cells induced by arsenic trioxide]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008;16:1021-5 pubmed