PPP2R1B

Summary

Gene Symbol: PPP2R1B
Description: protein phosphatase 2 scaffold subunit Abeta
Alias: PP2A-Abeta, PR65B, serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A beta isoform, PP2A, subunit A, PR65-beta isoform, PP2A, subunit A, R1-beta isoform, protein phosphatase 2 (formerly 2A), regulatory subunit A, beta isoform, protein phosphatase 2, regulatory subunit A, beta, protein phosphatase 2, structural/regulatory subunit A, beta
Species: human
Products:     PPP2R1B

Top Publications

  1. Wang S, Esplin E, Li J, Huang L, Gazdar A, Minna J, et al. Alterations of the PPP2R1B gene in human lung and colon cancer. Science. 1998;282:284-7 pubmed
    The PPP2R1B gene, which encodes the beta isoform of the A subunit of the serine/threonine protein phosphatase 2A (PP2A), was identified as a putative human tumor suppressor gene...
  2. Letourneux C, Rocher G, Porteu F. B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK. EMBO J. 2006;25:727-38 pubmed
    ..In addition, our results raise a new paradigm in ERK signaling in which ERK associated to a substrate can transphosphorylate nearby proteins. ..
  3. Nekhai S, Jerebtsova M, Jackson A, Southerland W. Regulation of HIV-1 transcription by protein phosphatase 1. Curr HIV Res. 2007;5:3-9 pubmed
    ..We also present a computer model of Tat-PP1 complex that might be useful for future drug design in anti-HIV-1 therapeutics. ..
  4. Ruediger R, Brewis N, Ohst K, Walter G. Increasing the ratio of PP2A core enzyme to holoenzyme inhibits Tat-stimulated HIV-1 transcription and virus production. Virology. 1997;238:432-43 pubmed
    ..These results demonstrate that the balance between PP2A holoenzyme and core enzyme is important for HIV-1 gene expression and virus production. ..
  5. Suo L, Zhou Y, Jia L, Wu H, Zheng J, Lyu Q, et al. Transcriptome profiling of human oocytes experiencing recurrent total fertilization failure. Sci Rep. 2018;8:17890 pubmed publisher
    ..KEGG analyses indicated down regulated genes in the Poly-PN group included oocyte meiosis related genes, such as PPP2R1B, YWHAZ, MAD2L1, SPDYC, SKP1 and CDC27, together with genes associated with RNA processing, such as SF3B1, ..
  6. Yu F, Yuan Y, Li D, Kou Y, Jiang B, Zhang P. The effect of lentivirus-mediated SIRT1 gene knockdown in the ATDC5 cell line via inhibition of the Wnt signaling pathway. Cell Signal. 2019;53:80-89 pubmed publisher
    ..some novel factors related to the Wnt signaling pathway after SIRT1 gene knockdown (BIRC3, IL1RAP, PPP3CA, PPP2R2A, PPP2R5E, GSN, PPP2R1B, etc), which might provide new clues in disease research related to chondrocyte degeneration.
  7. Su D, Zhang Q, Wang X, He P, Zhu Y, Zhao J, et al. Two types of human malignant melanoma cell lines revealed by expression patterns of mitochondrial and survival-apoptosis genes: implications for malignant melanoma therapy. Mol Cancer Ther. 2009;8:1292-304 pubmed publisher
    ..at higher levels in type A than in type B, whereas the different set of antiapoptotic (PSEN1, PPP2CA, API5, PPP2R1B, PPP2R1A, and FIS1), antioxidant (HSPD1, GSS, SOD1, ATOX1, and CAT), and proapoptotic (ENDOG, BAK1, CASP2, CASP4, ..
  8. Routila J, Mäkelä J, Luukkaa H, Leivo I, Irjala H, Westermarck J, et al. Potential role for inhibition of protein phosphatase 2A tumor suppressor in salivary gland malignancies. Genes Chromosomes Cancer. 2016;55:69-81 pubmed publisher
    ..Our genome-wide study showed that Ppp2r1b, a PP2A subunit encoding tumor suppressor gene, is underexpressed in submandibular gland tumors of Smgb-Tag mice...
  9. Godet A, Guergnon J, Croset A, Cayla X, Falanga P, Colle J, et al. PP2A1 binding, cell transducing and apoptotic properties of Vpr(77-92): a new functional domain of HIV-1 Vpr proteins. PLoS ONE. 2010;5:e13760 pubmed publisher
    ..In this context, future studies will be required to determine the functional relevance of the Vpr(77-92) domain in full length Vpr protein and also in entire HIV provirus. ..

More Information

Publications56

  1. Chen G, Tisayakorn S, Jorgensen C, D Ambrosio L, Goudreault M, Gingras A. PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4. J Biol Chem. 2008;283:29273-84 pubmed publisher
    ..PP4R3, and alpha4, and that the regulatory subunits of PP4c have evolved different modes of interaction with the catalytic subunit. ..
  2. 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. ..
  3. Griffiths D, Abdul Sada H, Knight L, Jackson B, Richards K, Prescott E, et al. Merkel cell polyomavirus small T antigen targets the NEMO adaptor protein to disrupt inflammatory signaling. J Virol. 2013;87:13853-67 pubmed publisher
    ..Together, these results highlight a novel function of MCPyV ST to subvert the innate immune response, allowing establishment of early or persistent infection within the host cell. ..
  4. 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. ..
  5. Yokoyama N, Reich N, Miller W. Involvement of protein phosphatase 2A in the interleukin-3-stimulated Jak2-Stat5 signaling pathway. J Interferon Cytokine Res. 2001;21:369-78 pubmed
    ..Our results suggest that PP2A plays a negative regulatory role in regulating the IL-3 signaling pathway via formation of complexes with Jak2 and Stat5. ..
  6. Hrimech M, Yao X, Branton P, Cohen E. Human immunodeficiency virus type 1 Vpr-mediated G(2) cell cycle arrest: Vpr interferes with cell cycle signaling cascades by interacting with the B subunit of serine/threonine protein phosphatase 2A. EMBO J. 2002;21:3918 pubmed
  7. Ruediger R, Pham H, Walter G. Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the A beta subunit gene. Oncogene. 2001;20:1892-9 pubmed
    ..Our findings may have important implications in regard to the role of PP2A as a tumor suppressor. ..
  8. Esplin E, Ramos P, Martinez B, Tomlinson G, Mumby M, Evans G. The glycine 90 to aspartate alteration in the Abeta subunit of PP2A (PPP2R1B) associates with breast cancer and causes a deficit in protein function. Genes Chromosomes Cancer. 2006;45:182-90 pubmed
    Mutations of the PPP2R1B gene, which encodes the Abeta scaffolding subunit of serine/threonine protein phosphatase 2A (PP2A), have been identified in several types of cancer including lung and breast carcinoma...
  9. Bucur O, Stancu A, Muraru M, Melet A, Petrescu S, Khosravi Far R. PLK1 is a binding partner and a negative regulator of FOXO3 tumor suppressor. Discoveries (Craiova). 2014;2: pubmed
    ..Furthermore, PLK1 can directly phosphorylate FOXO3 in an in vitro kinase assay. These results present the discovery of PLK1 proto-oncogene as a binding partner and a negative regulator of FOXO3 tumor suppressor. ..
  10. Baysal B, Willett Brozick J, Taschner P, Dauwerse J, Devilee P, Devlin B. A high-resolution integrated map spanning the SDHD gene at 11q23: a 1.1-Mb BAC contig, a partial transcript map and 15 new repeat polymorphisms in a tumour-suppressor region. Eur J Hum Genet. 2001;9:121-9 pubmed
    ..we provide integrated positional information for 33 ESTs and known genes, including KIAA1391, POU2AF1 (OBF1), PPP2R1B, CRYAB, HSPB2, DLAT, IL-18, PTPS, KIAA0781 and KAIA4591, which is mapped by NotI site cloning...
  11. Zhang Y, Talmon G, Wang J. MicroRNA-587 antagonizes 5-FU-induced apoptosis and confers drug resistance by regulating PPP2R1B expression in colorectal cancer. Cell Death Dis. 2015;6:e1845 pubmed publisher
    ..Further studies indicate that miR-587 modulates drug resistance through downregulation of expression of PPP2R1B, a regulatory subunit of the PP2A complex, which negatively regulates AKT activation...
  12. Lubert E, Sarge K. Interaction between protein phosphatase 2A and members of the importin beta superfamily. Biochem Biophys Res Commun. 2003;303:908-13 pubmed
    ..These results provide evidence that these importins can exist in a native complex with endogenous PP2A and that this serine/threonine phosphatase plays a role in regulating the nuclear import of NLS-containing proteins in vivo. ..
  13. Kim N, Kukkonen S, Gupta S, Aldovini A. Association of Tat with promoters of PTEN and PP2A subunits is key to transcriptional activation of apoptotic pathways in HIV-infected CD4+ T cells. PLoS Pathog. 2010;6:e1001103 pubmed publisher
    ..The Tat-PTEN and -PP2A promoter interactions provide a mechanistic explanation of Tat-mediated apoptosis in CD4+ T cells. ..
  14. Hendrix P, Mayer Jackel R, Cron P, Goris J, Hofsteenge J, Merlevede W, et al. Structure and expression of a 72-kDa regulatory subunit of protein phosphatase 2A. Evidence for different size forms produced by alternative splicing. J Biol Chem. 1993;268:15267-76 pubmed
    ..High levels of the PR72 mRNAs were detected in heart and muscle, while lower levels of PR130 transcripts were found in heart, brain, placenta, lung, muscle, and kidney. ..
  15. Kamibayashi C, Lickteig R, Estes R, Walter G, Mumby M. Expression of the A subunit of protein phosphatase 2A and characterization of its interactions with the catalytic and regulatory subunits. J Biol Chem. 1992;267:21864-72 pubmed
    ..These results suggest that each of the three subunits of protein phosphatase 2A forms direct contacts with both of the others. ..
  16. Takagi Y, Futamura M, Yamaguchi K, Aoki S, Takahashi T, Saji S. Alterations of the PPP2R1B gene located at 11q23 in human colorectal cancers. Gut. 2000;47:268-71 pubmed
    In 1998 the PPP2R1B gene encoding the A subunit of the serine/threonine protein phosphatase was identified as a putative tumour suppressor gene in lung and colon cancer in the chromosome region 11q22-24...
  17. Campbell I, Manolitsas T. Absence of PPP2R1B gene alterations in primary ovarian cancers. Oncogene. 1999;18:6367-9 pubmed
    The PPP2R1B gene has recently been implicated as a tumor suppressor based on the finding of somatic alterations in lung and colon cancers...
  18. Grinthal A, Adamovic I, Weiner B, Karplus M, Kleckner N. PR65, the HEAT-repeat scaffold of phosphatase PP2A, is an elastic connector that links force and catalysis. Proc Natl Acad Sci U S A. 2010;107:2467-72 pubmed publisher
    ..Given that helical-repeat proteins are involved in many cellular processes, the findings also encourage the view that mechanical forces may be of widespread importance. ..
  19. Takahashi M, Shibata H, Shimakawa M, Miyamoto M, Mukai H, Ono Y. Characterization of a novel giant scaffolding protein, CG-NAP, that anchors multiple signaling enzymes to centrosome and the golgi apparatus. J Biol Chem. 1999;274:17267-74 pubmed
  20. 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. ..
  21. Wallach T, Schellenberg K, Maier B, Kalathur R, Porras P, Wanker E, et al. Dynamic circadian protein-protein interaction networks predict temporal organization of cellular functions. PLoS Genet. 2013;9:e1003398 pubmed publisher
    ..Moreover, we predict that circadian PPIs dynamically connect many important cellular processes (signal transduction, cell cycle, etc.) contributing to temporal organization of cellular physiology in an unprecedented manner. ..
  22. Yang J, Fan G, Wadzinski B, Sakurai H, Richmond A. Protein phosphatase 2A interacts with and directly dephosphorylates RelA. J Biol Chem. 2001;276:47828-33 pubmed
    ..and Richmond, A. (2001) Cancer Res. 61, 4901-4909) could be due, at least in part, to the deficiency of PP2A, which exhibits decreased dephosphorylation of NF-kappa B/RelA. ..
  23. Guenebeaud C, Goldschneider D, Castets M, Guix C, Chazot G, Delloye Bourgeois C, et al. The dependence receptor UNC5H2/B triggers apoptosis via PP2A-mediated dephosphorylation of DAP kinase. Mol Cell. 2010;40:863-76 pubmed publisher
    ..Thus we show here that, in the absence of netrin-1, recruitment of PP2A to UNC5H2/B allows the activation of DAPk via a PP2A-mediated dephosphorylation and that this mechanism is involved in angiogenesis regulation. ..
  24. Dehde S, Rohaly G, Schub O, Nasheuer H, Bohn W, Chemnitz J, et al. Two immunologically distinct human DNA polymerase alpha-primase subpopulations are involved in cellular DNA replication. Mol Cell Biol. 2001;21:2581-93 pubmed
    ..The data indicate that the hypophosphorylated enzyme initiates DNA replication at origins, and the phosphorylated form synthesizes the primers for the lagging strand of the replication fork. ..
  25. 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. ..
  26. Tung H, de Rocquigny H, Zhao L, Cayla X, Roques B, Ozon R. Direct activation of protein phosphatase-2A0 by HIV-1 encoded protein complex NCp7:vpr. FEBS Lett. 1997;401:197-201 pubmed
  27. Strack S, Ruediger R, Walter G, Dagda R, Barwacz C, Cribbs J. Protein phosphatase 2A holoenzyme assembly: identification of contacts between B-family regulatory and scaffolding A subunits. J Biol Chem. 2002;277:20750-5 pubmed
    ..By expressing complementary charge-reversal mutants in neuronal PC6-3 cells, we further show that holoenzyme incorporation protects Bgamma from rapid degradation by the ubiquitin/proteasome pathway. ..
  28. Kalla C, Scheuermann M, Kube I, Schlotter M, Mertens D, Dohner H, et al. Analysis of 11q22-q23 deletion target genes in B-cell chronic lymphocytic leukaemia: evidence for a pathogenic role of NPAT, CUL5, and PPP2R1B. Eur J Cancer. 2007;43:1328-35 pubmed
    ..within 11q22-q23 by analysing NPAT (cell-cycle regulation), CUL5 (ubiquitin-dependent apoptosis regulation) and PPP2R1B (component of the cell-cycle and apoptosis regulating PP2A) for point mutations and their expression in B-CLL by ..
  29. Zolnierowicz S. Type 2A protein phosphatase, the complex regulator of numerous signaling pathways. Biochem Pharmacol. 2000;60:1225-35 pubmed
    ..Thus, a more thorough understanding of PP2A structure and function may lead to the development of novel strategies against human diseases. ..
  30. Leparc G, Mitra R. Non-EST-based prediction of novel alternatively spliced cassette exons with cell signaling function in Caenorhabditis elegans and human. Nucleic Acids Res. 2007;35:3192-202 pubmed
    ..Overall, PASE was able to uncover 59 novel alternative cassette exons in C. elegans and humans through a genome-wide ab initio prediction method that enriches for exons involved in signaling. ..
  31. Tamaki M, Goi T, Hirono Y, Katayama K, Yamaguchi A. PPP2R1B gene alterations inhibit interaction of PP2A-Abeta and PP2A-C proteins in colorectal cancers. Oncol Rep. 2004;11:655-9 pubmed
    The chromosome region 11q is frequently deleted in colorectal cancers. The PPP2R1B tumor suppressor gene, encoding the beta isoform of the A subunit of serine/threonine-specific protein phosphatase 2A (PP2A-Abeta), located at 11q22-23, ..
  32. Poretti G, Kwee I, Bernasconi B, Rancoita P, Rinaldi A, Capella C, et al. Chromosome 11q23.1 is an unstable region in B-cell tumor cell lines. Leuk Res. 2011;35:808-13 pubmed publisher
    ..Since no effect of the amplification at the local transcription level was observed, it is possible that 11q23 amplification might mainly represent the effect of unstable chromosomal region. ..
  33. Comandini A, Naro C, Adamo R, Akbar A, Lanna A, Bonmassar E, et al. Molecular mechanisms involved in HIV-1-Tat mediated inhibition of telomerase activity in human CD4(+) T lymphocytes. Mol Immunol. 2013;54:181-92 pubmed publisher
    ..These results suggest that in addition to inducing direct cell death, HIV infection may also reduce the replicative potential of non-infected CD4(+) T cells and this may contribute to the overall immunodeficiency in AIDS patients. ..
  34. Zhou J, Pham H, Ruediger R, Walter G. Characterization of the Aalpha and Abeta subunit isoforms of protein phosphatase 2A: differences in expression, subunit interaction, and evolution. Biochem J. 2003;369:387-98 pubmed
    ..Whereas both isoforms bound polyoma virus middle tumour antigen equally well, only Aalpha bound SV40 small tumour antigen. ..
  35. Yeh L, Hsieh Y, Chang J, Chang W, Chang C, Tsai F. Mutation analysis of the tumor suppressor gene PPP2R1B in human cervical cancer. Int J Gynecol Cancer. 2007;17:868-71 pubmed
    ..The PPP2R1B gene encodes the beta isoforms of the subunit A of the PP2A...
  36. Heikkinen P, Nummela M, Leivonen S, Westermarck J, Hill C, Kahari V, et al. Hypoxia-activated Smad3-specific dephosphorylation by PP2A. J Biol Chem. 2010;285:3740-9 pubmed publisher
    ..Our data demonstrate the existence of a Smad3-specific phosphatase and identify a novel role for PP2A. Moreover, our data implicate a novel mechanism by which hypoxia regulates growth factor responses. ..
  37. Vastiau A, Cao L, Jaspers M, Owsianik G, Janssens V, Cuppens H, et al. Interaction of the protein phosphatase 2A with the regulatory domain of the cystic fibrosis transmembrane conductance regulator channel. FEBS Lett. 2005;579:3392-6 pubmed
    ..Taken together our results show a direct and functional interaction between CFTR and PP2A. ..
  38. Adler H, Nallaseth F, Walter G, Tkachuk D. HRX leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A. J Biol Chem. 1997;272:28407-14 pubmed
    ..These results suggest that the leukemogenic effects of HRX fusion proteins may be related to interactions with SET and PP2A. ..
  39. Härmälä Braskén A, Mikhailov A, Söderström T, Meinander A, Holmström T, Damuni Z, et al. Type-2A protein phosphatase activity is required to maintain death receptor responsiveness. Oncogene. 2003;22:7677-86 pubmed
    ..The observed apoptosis suppression is likely to facilitate the tumor-promoting effect of a range of different type-2A protein phosphatase inhibitors, and could explain the reported tumor association of I2(PP2A). ..
  40. Wang F, Zou Y, Liu F, Yu X, Huang H, Zhang N, et al. Infrequent mutations of the PPP2R1A and PPP2R1B genes in patients with ovarian cancer. Mol Med Rep. 2013;7:1826-30 pubmed publisher
    Protein phosphatase 2, regulatory subunit A, ? (PPP2R1A) and ? (PPP2R1B) are paralogous subunits of the heterotrimeric protein phosphatase 2 (PP2A) holoenzyme that catalyzes the dephosphorylation of target substrate proteins...
  41. Yu C, Ji S, Sha Q, Sun Q, Fan H. CRL4-DCAF1 ubiquitin E3 ligase directs protein phosphatase 2A degradation to control oocyte meiotic maturation. Nat Commun. 2015;6:8017 pubmed publisher
    ..These results provide in vivo evidence that CRL4-directed PP2A-A degradation is physiologically essential for regulating oocyte meiosis and female fertility. ..
  42. Hemmings B, Adams Pearson C, Maurer F, Muller P, Goris J, Merlevede W, et al. alpha- and beta-forms of the 65-kDa subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure. Biochemistry. 1990;29:3166-73 pubmed
    ..The deduced protein sequences of the alpha- and beta-isotypes were found to be made up of 15 imperfect repeating units consisting of 39 amino acids. This repeating structure was conserved between species. ..
  43. Baysal B, Farr J, Goss J, Devlin B, Richard C. Genomic organization and precise physical location of protein phosphatase 2A regulatory subunit A beta isoform gene on chromosome band 11q23. Gene. 1998;217:107-16 pubmed
    ..Because the protein phosphatase 2 regulatory subunit A beta isoform gene (PPP2R1B) maps within the critical region of hereditary paraganglioma (PGL1) on chromosomal band 11q23, we characterized ..
  44. Chou H, Chen C, Lee H, Lee C, Huang G, Yang P, et al. Alterations of tumour suppressor gene PPP2R1B in hepatocellular carcinoma. Cancer Lett. 2007;253:138-43 pubmed
    To evaluate whether the tumour suppressor gene, PPP2R1B, is involved in pathogenesis of hepatocellular carcinoma (HCC), reverse transcription-polymerase chain reaction (RT-PCR) and cDNA sequencing were performed...
  45. 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. ..
  46. Riedel C, Katis V, Katou Y, Mori S, Itoh T, Helmhart W, et al. Protein phosphatase 2A protects centromeric sister chromatid cohesion during meiosis I. Nature. 2006;441:53-61 pubmed
    ..Our data are consistent with the notion that efficient cleavage of Rec8 requires phosphorylation of cohesin and that this is blocked by PP2A at meiosis I centromeres. ..
  47. Hemmer S, Wasenius V, Haglund C, Zhu Y, Knuutila S, Franssila K, et al. Alterations in the suppressor gene PPP2R1B in parathyroid hyperplasias and adenomas. Cancer Genet Cytogenet. 2002;134:13-7 pubmed
    ..A new potential suppressor gene PPP2R1B encoding the beta isoform of the A subunit of the serine/threorine protein phosphatase 2A was recently identified ..