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Enzyme Research
Volume 2012, Article ID 659649, 11 pages
http://dx.doi.org/10.1155/2012/659649
Review Article

Phosphatases: The New Brakes for Cancer Development?

Department of Systems Biology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA

Received 22 July 2011; Revised 25 August 2011; Accepted 20 September 2011

Academic Editor: Assia Shisheva

Copyright © 2012 Qingxiu Zhang and Francois X. Claret. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. T. F. Franke, D. R. Kaplan, and L. C. Cantley, “PI3K: downstream AKTion blocks apoptosis,” Cell, vol. 88, no. 4, pp. 435–437, 1997. View at Publisher · View at Google Scholar · View at Scopus
  2. B. T. Hennessy, D. L. Smith, P. T. Ram, Y. Lu, and G. B. Mills, “Exploiting the PI3K/AKT pathway for cancer drug discovery,” Nature Reviews Drug Discovery, vol. 4, no. 12, pp. 988–1004, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. A. Di Cristofano and P. P. Pandolfi, “The multiple roles of PTEN in tumor suppression,” Cell, vol. 100, no. 4, pp. 387–390, 2000. View at Google Scholar · View at Scopus
  4. C. Gewinner, Z. C. Wang, A. Richardson et al., “Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling,” Cancer Cell, vol. 16, no. 2, pp. 115–125, 2009. View at Publisher · View at Google Scholar · View at Scopus
  5. C. G. Fedele, L. M. Ooms, M. Ho et al., “Inositol polyphosphate 4-phosphatase II regulates PI3K/Akt signaling and is lost in human basal-like breast cancers,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 51, pp. 22231–22236, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Boudeau, G. Sapkota, and D. R. Alessi, “LKB1, a protein kinase regulating cell proliferation and polarity,” FEBS Letters, vol. 546, no. 1, pp. 159–165, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. D. J. Kwiatkowski, “Rhebbing up mTOR: new insights on TSC1 and TSC2, and the pathogenesis of tuberous sclerosis,” Cancer Biology & Therapy, vol. 2, no. 5, pp. 471–476, 2003. View at Google Scholar · View at Scopus
  8. B. D. Manning and L. C. Cantley, “United at last: the tuberous sclerosis complex gene products connect the phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) signalling,” Biochemical Society Transactions, vol. 31, no. 3, pp. 573–578, 2003. View at Publisher · View at Google Scholar · View at Scopus
  9. S. Avdulov, S. Li, V. Michalek et al., “Activation of translation complex eIF4F is essential for the genesis and maintenance of the malignant phenotype in human mammary epithelial cells,” Cancer Cell, vol. 5, no. 6, pp. 553–563, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. D. Ruggero, L. Montanaro, L. Ma et al., “The translation factor eIF-4E promotes tumor formation and cooperates with c-Myc in lymphomagenesis,” Nature Medicine, vol. 10, no. 5, pp. 484–486, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. H. G. Wendel, E. De Stanchina, J. S. Fridman et al., “Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy,” Nature, vol. 428, no. 6980, pp. 332–337, 2004. View at Publisher · View at Google Scholar · View at Scopus
  12. G. Manning, D. B. Whyte, R. Martinez, T. Hunter, and S. Sudarsanam, “The protein kinase complement of the human genome,” Science, vol. 298, no. 5600, pp. 1912–1934, 2002. View at Publisher · View at Google Scholar · View at Scopus
  13. Y. Shi, “Assembly and structure of protein phosphatase 2A,” Science in China, Series C, vol. 52, no. 2, pp. 135–146, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. T. A. Millward, S. Zolnierowicz, and B. A. Hemmings, “Regulation of protein kinase cascades by protein phosphatase 2A,” Trends in Biochemical Sciences, vol. 24, no. 5, pp. 186–191, 1999. View at Publisher · View at Google Scholar · View at Scopus
  15. T. Gao, F. Furnari, and A. C. Newton, “PHLPP: a phosphatase that directly dephosphorylates Akt, promotes apoptosis, and suppresses tumor growth,” Molecular Cell, vol. 18, no. 1, pp. 13–24, 2005. View at Publisher · View at Google Scholar · View at Scopus
  16. J. Brognard and A. C. Newton, “PHLiPPing the switch on Akt and protein kinase C signaling,” Trends in Endocrinology and Metabolism, vol. 19, no. 6, pp. 223–230, 2008. View at Publisher · View at Google Scholar · View at Scopus
  17. A. Di Cristofano, B. Pesce, C. Cordon-Cardo, and P. P. Pandolfi, “Pten is essential for embryonic development and tumour suppression,” Nature Genetics, vol. 19, no. 4, pp. 348–355, 1998. View at Publisher · View at Google Scholar · View at Scopus
  18. V. Stambolic, A. Suzuki, J. L. De la Pompa et al., “Negative regulation of PKB/Akt-dependent cell survival by the tumor suppressor PTEN,” Cell, vol. 95, no. 1, pp. 29–39, 1998. View at Publisher · View at Google Scholar · View at Scopus
  19. X. Wu, K. Senechal, M. S. Neshat, Y. E. Whang, and C. L. Sawyers, “The PTEN/MMAC1 tumor suppressor phosphatase functions as a negative regulator of the phosphoinositide 3-kinase/Akt pathway,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 26, pp. 15587–15591, 1998. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Li, C. Yen, D. Liaw et al., “PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer,” Science, vol. 275, no. 5308, pp. 1943–1947, 1997. View at Publisher · View at Google Scholar · View at Scopus
  21. P. A. Steck, M. A. Pershouse, S. A. Jasser et al., “Identification of a candidate tumour suppressor gene, MMAC1, at chromosome 10q23.3 that is mutated in multiple advanced cancers,” Nature Genetics, vol. 15, no. 4, pp. 356–362, 1997. View at Publisher · View at Google Scholar · View at Scopus
  22. D. M. Li and H. Sun, “TEP1, encoded by a candidate tumor suppressor locus, is a novel protein tyrosine phosphatase regulated by transforming growth factor β,” Cancer Research, vol. 57, no. 11, pp. 2124–2129, 1997. View at Google Scholar · View at Scopus
  23. D. Liaw, D. J. Marsh, J. Li et al., “Germline mutations of the PTEN gene in Cowden disease, an inherited breast and thyroid cancer syndrome,” Nature Genetics, vol. 16, no. 1, pp. 64–67, 1997. View at Google Scholar · View at Scopus
  24. D. J. Marsh, P. L. Dahia, Z. Zheng et al., “Germline mutations in PTEN are present in Bannayan-Zonana syndrome,” Nature Genetics, vol. 16, no. 4, pp. 333–334, 1997. View at Google Scholar · View at Scopus
  25. I. Sansal and W. R. Sellers, “The biology and clinical relevance of the PTEN tumor suppressor pathway,” Journal of Clinical Oncology, vol. 22, no. 14, pp. 2954–2963, 2004. View at Publisher · View at Google Scholar · View at Scopus
  26. N. Terakawa, Y. Kanamori, and S. Yoshida, “Loss of PTEN expression followed by Akt phosphorylation is a poor prognostic factor for patients with endometrial cancer,” Endocrine-Related Cancer, vol. 10, no. 2, pp. 203–208, 2003. View at Publisher · View at Google Scholar · View at Scopus
  27. H. Wu, V. Goel, and F. G. Haluska, “PTEN signaling pathways in melanoma,” Oncogene, vol. 22, no. 20, pp. 3113–3122, 2003. View at Publisher · View at Google Scholar · View at Scopus
  28. K. Stemke-Hale, A. M. Gonzalez-Angulo, A. Lluch et al., “An integrative genomic and proteomic analysis of PIK3CA, PTEN, and AKT mutations in breast cancer,” Cancer Research, vol. 68, no. 15, pp. 6084–6091, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. A. M. Gonzalez-Angulo, J. Ferrer-Lozano, K. Stemke-Hale et al., “PI3K pathway mutations and PTEN levels in primary and metastatic breast cancer,” Molecular Cancer Therapeutics, vol. 10, no. 6, pp. 1093–1101, 2011. View at Publisher · View at Google Scholar
  30. S. Regina, J. B. Valentin, S. Lachot, E. Lemarié, J. Rollin, and Y. Gruel, “Increased tissue factor expression is associated with reduced survival in non-small cell lung cancer and with mutations of TP53 and PTEN,” Clinical Chemistry, vol. 55, no. 10, pp. 1834–1842, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. E. Forgacs, E. J. Biesterveld, Y. Sekido et al., “Mutation analysis of the PTEN/MMAC1 gene in lung cancer,” Oncogene, vol. 17, no. 12, pp. 1557–1565, 1998. View at Google Scholar · View at Scopus
  32. Y. Hosoya, A. Gemma, M. Seike et al., “Alteration of the PTEN/MMAC1 gene locus in primary lung cancer with distant metastasis,” Lung Cancer, vol. 25, no. 2, pp. 87–93, 1999. View at Publisher · View at Google Scholar · View at Scopus
  33. H. Suzuki, D. Freije, D. R. Nusskern et al., “Interfocal heterogeneity of PTEN/MMAC1 gene alterations in multiple metastatic prostate cancer tissues,” Cancer Research, vol. 58, no. 2, pp. 204–209, 1998. View at Google Scholar · View at Scopus
  34. F. A. Norris, E. Ungewickell, and P. W. Majerus, “Inositol hexakisphosphate binds to clathrin assembly protein 3 (AP-3/AP180) and inhibits clathrin cage assembly in vitro,” The Journal of Biological Chemistry, vol. 270, no. 1, pp. 214–217, 1995. View at Publisher · View at Google Scholar · View at Scopus
  35. F. A. Norris, R. C. Atkins, and P. W. Majerus, “The cDNA cloning and characterization of inositol polyphosphate 4-phosphatase type II. Evidence for conserved alternative splicing in the 4-phosphatase family,” The Journal of Biological Chemistry, vol. 272, no. 38, pp. 23859–23864, 1997. View at Publisher · View at Google Scholar · View at Scopus
  36. M. Ferron and J. Vacher, “Characterization of the murine Inpp4b gene and identification of a novel isoform,” Gene, vol. 376, no. 1-2, pp. 152–161, 2006. View at Publisher · View at Google Scholar · View at Scopus
  37. T. F. Westbrook, E. S. Martin, M. R. Schlabach et al., “A genetic screen for candidate tumor suppressors identifies REST,” Cell, vol. 121, no. 6, pp. 837–848, 2005. View at Publisher · View at Google Scholar · View at Scopus
  38. S. Barnache, E. Le Scolan, O. Kosmider, N. Denis, and F. Moreau-Gachelin, “Phosphatidylinositol 4-phosphatase type II is an erythropoietin-responsive gene,” Oncogene, vol. 25, no. 9, pp. 1420–1423, 2006. View at Publisher · View at Google Scholar · View at Scopus
  39. T. L. Naylor, J. Greshock, Y. Wang et al., “High resolution genomic analysis of sporadic breast cancer using array-based comparative genomic hybridization,” Breast Cancer Research, vol. 7, no. 6, pp. R1186–R1198, 2005. View at Google Scholar
  40. A. Bergamaschi, Y. H. Kim, P. Wang et al., “Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer,” Genes Chromosomes and Cancer, vol. 45, no. 11, pp. 1033–1040, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. S. F. Chin, Y. Wang, N. P. Thorne et al., “Using array-comparative genomic hybridization to define molecular portraits of primary breast cancers,” Oncogene, vol. 26, no. 13, pp. 1959–1970, 2007. View at Publisher · View at Google Scholar · View at Scopus
  42. E. A. Rakha, S. E. El-Sheikh, M. A. Kandil, M. E. El-Sayed, A. R. Green, and I. O. Ellis, “Expression of BRCA1 protein in breast cancer and its prognostic significance,” Human Pathology, vol. 39, no. 6, pp. 857–865, 2008. View at Publisher · View at Google Scholar · View at Scopus
  43. Y. Wang, J. I. Kreisberg, and P. M. Ghosh, “Cross-talk between the androgen receptor and the phosphatidylinositol 3-kinase/Akt pathway in prostate cancer,” Current Cancer Drug Targets, vol. 7, no. 6, pp. 591–604, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. T. L. Yuan and L. C. Cantley, “PI3K pathway alterations in cancer: variations on a theme,” Oncogene, vol. 27, no. 41, pp. 5497–5510, 2008. View at Publisher · View at Google Scholar · View at Scopus
  45. M. C. Hodgson, L.-J. Shao, A. Frolov et al., “Decreased expression and androgen regulation of the tumor suppressor gene INPP4B in prostate cancer,” Cancer Research, vol. 71, no. 2, pp. 572–582, 2011. View at Publisher · View at Google Scholar
  46. I. U. Agoulnik, M. C. Hodgson, W. A. Bowden, and M. M. Ittmann, “INPP4B: the new kid on the PI3K block,” Oncotarget, vol. 2, no. 4, pp. 321–328, 2011. View at Google Scholar
  47. J. E. Damen, L. Liu, P. Rosten et al., “The 145-kDa protein induced to associate with She by multiple cytokines is an inositol tetraphosphate and phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 4, pp. 1689–1693, 1996. View at Google Scholar · View at Scopus
  48. M. D. Ware, P. Rosten, J. E. Damen, L. Liu, R. K. Humphries, and G. Krystal, “Cloning and characterization of human SHIP, the 145-kD inositol 5-phosphatase that associates with SHC after cytokine stimulation,” Blood, vol. 88, no. 8, pp. 2833–2840, 1996. View at Google Scholar · View at Scopus
  49. W. G. Kerr, M. Heller, and L. A. Herzenberg, “Analysis of lipopolysaccharide-response genes in B-lineage cells demonstrates that they can have differentiation stage-restricted expression and contain SH2 domains,” Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 9, pp. 3947–3952, 1996. View at Publisher · View at Google Scholar · View at Scopus
  50. M. N. Lioubin, P. A. Algate, S. Tsai, K. Carlberg, R. Aebersold, and L. R. Rohrschneider, “p150Ship, a signal transduction molecule with inositol polyphosphate-5-phosphatase activity,” Genes and Development, vol. 10, no. 9, pp. 1084–1095, 1996. View at Google Scholar · View at Scopus
  51. A. Zippo, A. De Robertis, M. Bardelli, F. Galvagni, and S. Oliviero, “Identification of Flk-1 target genes in vasculogenesis: Pim-1 is required for endothelial and mural cell differentiation in vitro,” Blood, vol. 103, no. 12, pp. 4536–4544, 2004. View at Publisher · View at Google Scholar · View at Scopus
  52. Z. Tu, J. M. Ninos, Z. Ma et al., “Embryonic and hematopoietic stem cells express a novel SH2-containing inositol 5-phosphatase isoform that partners with the Grb2 adapter protein,” Blood, vol. 98, no. 7, pp. 2028–2038, 2001. View at Publisher · View at Google Scholar · View at Scopus
  53. N. Gupta, A. M. Scharenberg, D. A. Fruman, L. C. Cantley, J. P. Kinet, and E. O. Long, “The SH2 domain-containing inositol 5-phosphatase (SHIP) recruits the p85 subunit of phosphoinositide 3-kinase during FcγRIIb1-mediated inhibition of B cell receptor signaling,” The Journal of Biological Chemistry, vol. 274, no. 11, pp. 7489–7494, 1999. View at Publisher · View at Google Scholar · View at Scopus
  54. D. M. Lucas and L. R. Rohrschneider, “A novel spliced form of SH2-containing inositol phosphatase is expressed during myeloid development,” Blood, vol. 93, no. 6, pp. 1922–1933, 1999. View at Google Scholar · View at Scopus
  55. L. Liu, J. E. Damen, M. D. Ware, and G. Krystal, “Interleukin-3 induces the association of the inositol 5-phosphatase SHIP with SHP2,” The Journal of Biological Chemistry, vol. 272, no. 17, pp. 10998–11001, 1997. View at Publisher · View at Google Scholar · View at Scopus
  56. R. L. Cutler, L. Liu, J. E. Damen, and G. Krystal, “Multiple cytokines induce the tyrosine phosphorylation of Shc and its association with Grb2 in hemopoietic cells,” The Journal of Biological Chemistry, vol. 268, no. 29, pp. 21463–21465, 1993. View at Google Scholar · View at Scopus
  57. M. N. Lioubin, G. M. Myles, K. Carlberg, D. Bowtell, and L. R. Rohrschneider, “Shc, Grb2, Sos1, and a 150-kilodalton tyrosine-phosphorylated protein form complexes with Fms in hematopoietic cells,” Molecular and Cellular Biology, vol. 14, no. 9, pp. 5682–5691, 1994. View at Google Scholar · View at Scopus
  58. L. M. Sly, V. Ho, F. Antignano et al., “The role of SHIP in macrophages,” Frontiers in Bioscience, vol. 12, pp. 2836–2848, 2007. View at Publisher · View at Google Scholar · View at Scopus
  59. C. P. Baran, S. Tridandapani, C. D. Helgason, R. K. Humphries, G. Krystal, and C. B. Marsh, “The inositol 5-phosphatase SHIP-1 and the Src kinase Lyn negatively regulate macrophage colony-stimulating factor-induced Akt activity,” The Journal of Biological Chemistry, vol. 278, no. 40, pp. 38628–38636, 2003. View at Publisher · View at Google Scholar · View at Scopus
  60. C. D. Helgason, J. E. Damen, P. Rosten et al., “Targeted disruption of SHIP leads to hemopoietic perturbations, lung pathology, and a shortened life span,” Genes and Development, vol. 12, no. 11, pp. 1610–1620, 1998. View at Google Scholar · View at Scopus
  61. P. Zhou, H. Kitaura, S. L. Teitelbaum, G. Krystal, F. P. Ross, and S. Takeshita, “SHIP1 negatively regulates proliferation of osteoclast precursors via Akt-dependent alterations in D-type cyclins and p27,” Journal of Immunology, vol. 177, no. 12, pp. 8777–8784, 2006. View at Google Scholar · View at Scopus
  62. A. V. Miletic, A. N. Anzelon-Mills, D. M. Mills et al., “Coordinate suppression of B cell lymphoma by PTEN and SHIP phosphatases,” The Journal of Experimental Medicine, vol. 207, no. 11, pp. 2407–2420, 2010. View at Publisher · View at Google Scholar · View at Scopus
  63. L. M. Sly, M. J. Rauh, J. Kalesnikoff, T. Büchse, and G. Krystal, “SHIP, SHIP2, and PTEN activities are regulated in vivo by modulation of their protein levels: SHIP is up-regulated in macrophages and mast cells by lipopolysaccharide,” Experimental Hematology, vol. 31, no. 12, pp. 1170–1181, 2003. View at Publisher · View at Google Scholar · View at Scopus
  64. S. Schurmans, R. Carrió, J. Behrends, V. Pouillon, J. Merino, and S. Clément, “The mouse SHIP2 (Inppl1) gene: complementary DNA, genomic structure, promoter analysis, and gene expression in the embryo and adult mouse,” Genomics, vol. 62, no. 2, pp. 260–271, 1999. View at Publisher · View at Google Scholar · View at Scopus
  65. S. Clément, U. Krause, F. Desmedt et al., “The lipid phosphatase SHIP2 controls insulin sensitivity,” Nature, vol. 409, no. 6816, pp. 92–97, 2001. View at Publisher · View at Google Scholar · View at Scopus
  66. N. K. Prasad, M. Tandon, A. Handa et al., “High expression of obesity-linked phosphatase SHIP2 in invasive breast cancer correlates with reduced disease-free survival,” Tumor Biology, vol. 29, no. 5, pp. 330–341, 2008. View at Publisher · View at Google Scholar · View at Scopus
  67. N. K. Prasad, M. Tandon, S. Badve, P. W. Snyder, and H. Nakshatri, “Phosphoinositol phosphatase SHIP2 promotes cancer development and metastasis coupled with alterations in EGF receptor turnover,” Carcinogenesis, vol. 29, no. 1, pp. 25–34, 2008. View at Publisher · View at Google Scholar · View at Scopus
  68. J. Yu, D. G. Ryan, S. Getsios, M. Oliveira-Fernandes, A. Fatima, and R. M. Lavker, “MicroRNA-184 antagonizes microRNA-205 to maintain SHIP2 levels in epithelia,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 49, pp. 19300–19305, 2008. View at Publisher · View at Google Scholar · View at Scopus
  69. Y. Barrandon and H. Green, “Cell migration is essential for sustained growth of keratinocyte colonies: the roles of transforming growth factor-α and epidermal growth factor,” Cell, vol. 50, no. 7, pp. 1131–1137, 1987. View at Google Scholar · View at Scopus
  70. J. Yu, H. Peng, Q. Ruan, A. Fatima, S. Getsios, and R. M. Lavker, “MicroRNA-205 promotes keratinocyte migration via the lipid phosphatase SHIP2,” The FASEB Journal, vol. 24, no. 10, pp. 3950–3959, 2010. View at Publisher · View at Google Scholar · View at Scopus
  71. X. H. Lin, J. Walter, K. Scheidtmann, K. Ohst, J. Newport, and G. Walter, “Protein phosphatase 2A is required for the initiation of chromosomal DNA replication,” Proceedings of the National Academy of Sciences of the United States of America, vol. 95, no. 25, pp. 14693–14698, 1998. View at Publisher · View at Google Scholar · View at Scopus
  72. R. Ruediger, M. Hentz, J. Fait, M. Mumby, and G. Walter, “Molecular model of the A subunit of protein phosphatase 2A: interaction with other subunits and tumor antigens,” Journal of Virology, vol. 68, no. 1, pp. 123–129, 1994. View at Google Scholar · View at Scopus
  73. X. X. Yu, X. Du, C. S. Moreno et al., “Methylation of the protein phosphatase 2A catalytic subunit is essential for association of Bα regulatory subunit but not SG2NA, striatin, or polyomavirus middle tumor antigen,” Molecular Biology of the Cell, vol. 12, no. 1, pp. 185–199, 2001. View at Google Scholar · View at Scopus
  74. B. McCright, A. R. Brothman, and D. M. Virshup, “Assignment of human protein phosphatase 2A regulatory subunit genes B56α, B56β, B56γ, B56δ, and B56ε (PPP2R5A-PPP2R5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2 → p12,” Genomics, vol. 36, no. 1, pp. 168–170, 1996. View at Publisher · View at Google Scholar · View at Scopus
  75. U. S. Cho, S. Morrone, A. A. Sablina, J. D. Arroyo, W. C. Hahn, and W. Xu, “Structural basis of PP2A inhibition by small t antigen,” PLoS Biology, vol. 5, no. 8, p. e202, 2007. View at Publisher · View at Google Scholar · View at Scopus
  76. D. M. Virshup and S. Shenolikar, “From promiscuity to precision: protein phosphatases get a makeover,” Molecular Cell, vol. 33, no. 5, pp. 537–545, 2009. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Chen, B. L. Martin, and D. L. Brautigan, “Regulation of protein serine-threonine phosphatase type-2A by tyrosine phosphorylation,” Science, vol. 257, no. 5074, pp. 1261–1264, 1992. View at Google Scholar · View at Scopus
  78. C. Letourneux, G. Rocher, and F. Porteu, “B56-containing PP2A dephosphorylate ERK and their activity is controlled by the early gene IEX-1 and ERK,” The EMBO Journal, vol. 25, no. 4, pp. 727–738, 2006. View at Publisher · View at Google Scholar · View at Scopus
  79. M. Mumby, “PP2A: unveiling a reluctant tumor suppressor,” Cell, vol. 130, no. 1, pp. 21–24, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. J. D. Arroyo and W. C. Hahn, “Involvement of PP2A in viral and cellular transformation,” Oncogene, vol. 24, no. 52, pp. 7746–7755, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. P. J. A. Eichhorn, M. P. Creyghton, and R. Bernards, “Protein phosphatase 2A regulatory subunits and cancer,” Biochimica et Biophysica Acta, vol. 1795, no. 1, pp. 1–15, 2009. View at Publisher · View at Google Scholar · View at Scopus
  82. M. Suganuma, H. Fujiki, H. Suguri et al., “Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter,” Proceedings of the National Academy of Sciences of the United States of America, vol. 85, no. 6, pp. 1768–1771, 1988. View at Publisher · View at Google Scholar · View at Scopus
  83. A. Ito, Y. I. Koma, and K. Watabe, “A mutation in protein phosphatase type 2A as a cause of melanoma progression,” Histology and Histopathology, vol. 18, no. 4, pp. 1313–1319, 2003. View at Google Scholar · View at Scopus
  84. W. C. Hahn, S. K. Dessain, M. W. Brooks et al., “Enumeration of the simian virus 40 early region elements necessary for human cell transformation,” Molecular and Cellular Biology, vol. 22, no. 7, pp. 2111–2123, 2002. View at Publisher · View at Google Scholar · View at Scopus
  85. J. Yu, A. Boyapati, and K. Rundell, “Critical role for SV40 small-t antigen in human cell transformation,” Virology, vol. 290, no. 2, pp. 192–198, 2001. View at Publisher · View at Google Scholar · View at Scopus
  86. A. H. Schönthal, “Role of serine/threonine protein phosphatase 2A in cancer,” Cancer Letters, vol. 170, no. 1, pp. 1–13, 2001. View at Publisher · View at Google Scholar · View at Scopus
  87. W. Chen, R. Possemato, K. T. Campbell, C. A. Plattner, D. C. Pallas, and W. C. Hahn, “Identification of specific PP2A complexes involved in human cell transformation,” Cancer Cell, vol. 5, no. 2, pp. 127–136, 2004. View at Publisher · View at Google Scholar · View at Scopus
  88. K. M. Dohoney, C. Guillerm, C. Whiteford et al., “Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage,” Oncogene, vol. 23, no. 1, pp. 49–57, 2004. View at Publisher · View at Google Scholar · View at Scopus
  89. H. H. Li, X. Cai, G. P. Shouse, L. G. Piluso, and X. Liu, “A specific PP2A regulatory subunit, B56γ, mediates DNA damage-induced dephosphorylation of p53 at Thr55,” The EMBO Journal, vol. 26, no. 2, pp. 402–411, 2007. View at Publisher · View at Google Scholar · View at Scopus
  90. A. A. Sablina, M. Hector, N. Colpaert, and W. C. Hahn, “Identification of PP2A complexes and pathways involved in cell transformation,” Cancer Research, vol. 70, no. 24, pp. 10474–10484, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. S. S. Wang, E. D. Esplin, J. L. Li et al., “Alterations of the PPP2R1B gene in human lung and colon cancer,” Science, vol. 282, no. 5387, pp. 284–287, 1998. View at Publisher · View at Google Scholar · View at Scopus
  92. G. A. Calin, M. G. Di Iasio, E. Caprini et al., “Low frequency of alterations of the α (PPP2R1A) and β (PPP2R1B) isoforms of the subunit A of the serine-threonine phosphatase 2A in human neoplasms,” Oncogene, vol. 19, no. 9, pp. 1191–1195, 2000. View at Google Scholar · View at Scopus
  93. R. Ruediger, H. T. Pham, and G. Walter, “Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the Aβ subunit gene,” Oncogene, vol. 20, no. 15, pp. 1892–1899, 2001. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Tamaki, T. Goi, Y. Hirono, K. Katayama, and A. Yamaguchi, “PPP2R1B gene alterations inhibit interaction of PP2A-Abeta and PP2A-C proteins in colorectal cancers,” Oncology Reports, vol. 11, no. 3, pp. 655–659, 2004. View at Google Scholar · View at Scopus
  95. R. Ruediger, H. T. Pham, and G. Walter, “Disruption of protein phosphatase 2a subunit interaction in human cancers with mutations in the Aα subunit gene,” Oncogene, vol. 20, no. 1, pp. 10–15, 2001. View at Google Scholar · View at Scopus
  96. B. E. Baysal, J. E. Willett-Brozick, P. E. M. Taschner, J. G. Dauwerse, P. Devilee, and B. Devlin, “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,” European Journal of Human Genetics, vol. 9, no. 2, pp. 121–129, 2001. View at Google Scholar · View at Scopus
  97. S. Jones, T. L. Wang, I. M. Shih et al., “Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma,” Science, vol. 330, no. 6001, pp. 228–231, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. M. K. McConechy, M. S. Anglesio, S. E. Kalloger et al., “Subtype-specific mutation of PPP2R1A in endometrial and ovarian carcinomas,” Journal of Pathology, vol. 223, no. 5, pp. 567–573, 2011. View at Publisher · View at Google Scholar
  99. L. F. Grochola, A. Vazquez, E. E. Bond et al., “Recent natural selection identifies a genetic variant in a regulatory subunit of protein phosphatase 2A that associates with altered cancer risk and survival,” Clinical Cancer Research, vol. 15, no. 19, pp. 6301–6308, 2009. View at Publisher · View at Google Scholar · View at Scopus
  100. M. Li, A. Makkinje, and Z. Damuni, “The myeloid leukemia-associated protein SET is a potent inhibitor of protein phosphatase 2A,” The Journal of Biological Chemistry, vol. 271, no. 19, pp. 11059–11062, 1996. View at Publisher · View at Google Scholar · View at Scopus
  101. M. von Lindern, S. van Baal, J. Wiegant, A. Raap, A. Hagemeijer, and G. Grosveld, “can, a putative oncogene associated with myeloid leukemogenesis, may be activated by fusion of its 3 half to different genes: characterization of the set gene,” Molecular and Cellular Biology, vol. 12, no. 8, pp. 3346–3355, 1992. View at Google Scholar · View at Scopus
  102. G. P. Shouse, Y. Nobumori, and X. Liu, “A B56γ mutation in lung cancer disrupts the p53-dependent tumor-suppressor function of protein phosphatase 2A,” Oncogene, vol. 29, no. 27, pp. 3933–3941, 2010. View at Publisher · View at Google Scholar · View at Scopus
  103. Z. Jin, L. Wallace, S. Q. Harper, and J. Yang, “PP2A:B56ε, a substrate of caspase-3, regulates p53-dependent and p53-independent apoptosis during development,” The Journal of Biological Chemistry, vol. 285, no. 45, pp. 34493–34502, 2010. View at Publisher · View at Google Scholar · View at Scopus
  104. J. M. Seeling, J. R. Miller, R. Gil, R. T. Moon, R. White, and D. M. Virshup, “Regulation of β-catenin signaling by the B56 subunit of protein phosphatase 2A,” Science, vol. 283, no. 5410, pp. 2089–2091, 1999. View at Publisher · View at Google Scholar · View at Scopus
  105. Z. H. Gao, J. M. Seeling, V. Hill, A. Yochum, and D. M. Virshup, “Casein kinase I phosphorylates and destabilizes the β-catenin degradation complex,” Proceedings of the National Academy of Sciences of the United States of America, vol. 99, no. 3, pp. 1182–1187, 2002. View at Publisher · View at Google Scholar · View at Scopus
  106. X. Li, H. J. Yost, D. M. Virshup, and J. M. Seeling, “Protein phosphatase 2A and its B56 regulatory subunit inhibit Wnt signaling in Xenopus,” The EMBO Journal, vol. 20, no. 15, pp. 4122–4131, 2001. View at Publisher · View at Google Scholar · View at Scopus
  107. J. Yang, J. Wu, C. Tan, and P. S. Klein, “PP2A: B56E is required for Wnt/β-catenin signaling during embryonic development,” Development, vol. 130, no. 23, pp. 5569–5578, 2003. View at Publisher · View at Google Scholar · View at Scopus
  108. X. He, M. Semenov, K. Tamai, and X. Zeng, “LDL receptor-related proteins 5 and 6 in Wnt/β-catenin signaling: arrows point the way,” Development, vol. 131, no. 8, pp. 1663–1677, 2004. View at Publisher · View at Google Scholar · View at Scopus
  109. B. T. MacDonald, K. Tamai, and X. He, “Wnt/β-catenin signaling: components, mechanisms, and diseases,” Developmental Cell, vol. 17, no. 1, pp. 9–26, 2009. View at Publisher · View at Google Scholar · View at Scopus
  110. E. Yeh, M. Cunningham, H. Arnold et al., “A signalling pathway controlling c-Myc degradation that impacts oncogenic transformation of human cells,” Nature Cell Biology, vol. 6, no. 4, pp. 308–318, 2004. View at Publisher · View at Google Scholar · View at Scopus
  111. H. K. Arnold and R. C. Sears, “Protein phosphatase 2A regulatory subunit B56α associates with c-Myc and negatively regulates c-Myc accumulation,” Molecular and Cellular Biology, vol. 26, no. 7, pp. 2832–2844, 2006. View at Publisher · View at Google Scholar · View at Scopus
  112. M. R. Junttila, P. Puustinen, M. Niemelä et al., “CIP2A inhibits PP2A in human malignancies,” Cell, vol. 130, no. 1, pp. 51–62, 2007. View at Publisher · View at Google Scholar · View at Scopus
  113. S. S. Margolis, J. A. Perry, C. M. Forester et al., “Role for the PP2A/B56δ phosphatase in regulating 14-3-3 release from Cdc25 to control mitosis,” Cell, vol. 127, no. 4, pp. 759–773, 2006. View at Publisher · View at Google Scholar · View at Scopus
  114. C. M. Forester, J. Maddox, J. V. Louis, J. Goris, and D. M. Virshup, “Control of mitotic exit by PP2A regulation of Cdc25C and Cdk1,” Proceedings of the National Academy of Sciences of the United States of America, vol. 104, no. 50, pp. 19867–19872, 2007. View at Publisher · View at Google Scholar · View at Scopus
  115. G. Rocher, C. Letourneux, P. Lenormand, and F. Porteu, “Inhibition of B56-containing protein phosphatase 2As by the early response gene IEX-1 leads to control of Akt activity,” The Journal of Biological Chemistry, vol. 282, no. 8, pp. 5468–5477, 2007. View at Publisher · View at Google Scholar · View at Scopus
  116. M. X. Wu, “Roles of the stress-induced gene IEX-1 in regulation of cell death and oncogenesis,” Apoptosis, vol. 8, no. 1, pp. 11–18, 2003. View at Publisher · View at Google Scholar · View at Scopus
  117. N. Vereshchagina, M. C. Ramel, E. Bitoun, and C. Wilson, “The protein phosphatase PP2A-B subunit Widerborst is a negative regulator of cytoplasmic activated Akt and lipid metabolism in Drosophila,” Journal of Cell Science, vol. 121, no. 20, pp. 3383–3392, 2008. View at Publisher · View at Google Scholar · View at Scopus
  118. J. T. Rodgers, R. O. Vogel, and P. Puigserver, “Clk2 and B56β mediate insulin-regulated assembly of the PP2A phosphatase holoenzyme complex on Akt,” Molecular Cell, vol. 41, no. 4, pp. 471–479, 2011. View at Publisher · View at Google Scholar
  119. K. J. Mavrakis, A. L. Wolfe, E. Oricchio et al., “Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia,” Nature Cell Biology, vol. 12, no. 4, pp. 372–379, 2010. View at Publisher · View at Google Scholar · View at Scopus