Top

Published in:

01-06-2008

SV40 small T antigen and PP2A phosphatase in cell transformation

Authors: Anna A. Sablina, William C. Hahn

Published in: Cancer and Metastasis Reviews | Issue 2/2008

Abstract

The SV40 early region protein, SV40 small t antigen, promotes cell transformation through negative regulation of the protein phosphatase 2A (PP2A) family of serine–threonine phosphatases. More recently, reduced levels of PP2A activity have been found in different types of human cancer. This occurs either through inactivating mutations of PP2A structural subunits, or by upregulation of the cellular PP2A inhibitors, CIP2A and SET. Several distinct PP2A complexes have been identified that contribute directly to tumor suppression by regulating specific phosphorylation events. These studies provide us with new insights into the role of protein phosphatases in cancer initiation and maintenance.

Hahn, W. C., Dessain, S. K., Brooks, M. W., King, J. E., Elenbaas, B., Sabatini, D. M., et al. (2002). Enumeration of the simian virus 40 early region elements necessary for human cell transformation. Molecular and Cellular Biology, 22(7), 2111–2123.PubMedCrossRef

Kleinberger, T., & Shenk, T. (1993). Adenovirus e4orf4 protein binds to protein phosphatase 2A, and the complex down regulates e1a-enhanced Junb transcription. Journal of Virology, 67(12), 7556–7560.PubMed

Pallas, D. C., Shahrik, L. K., Martin, B. L., Jaspers, S., Miller, T. B., Brautigan, D. L., et al. (1990). Polyoma small and middle t antigens and SV40 small t antigen form stable complexes with protein phosphatase 2A. Cell, 60(1), 167–176.PubMedCrossRef

Rundell, K. (1987). Complete interaction of cellular 56,000- and 32,000-mr proteins with simian virus 40 small-t antigen in productively infected cells. Journal of Virology, 61(4), 1240–1243.PubMed

Yu, J., Boyapati, A., & Rundell, K. (2001). Critical role for SV40 small-t antigen in human cell transformation. Virology, 290(2), 192–198.PubMedCrossRef

Calin, G. A., Di Iasio, M. G., Caprini, E., Vorechovsky, I., Natali, P. G., Sozzi, G., et al. (2000). Low frequency of alterations of the alpha (PPP2r1A) and beta (PPP2r1B) isoforms of the subunit a of the serine–threonine phosphatase 2A in human neoplasms. Oncogene, 19(9), 1191–1195.PubMedCrossRef

Takagi, Y., Futamura, M., Yamaguchi, K., Aoki, S., Takahashi, T., & Saji, S. (2000). Alterations of the PPP2r1B gene located at 11q23 in human colorectal cancers. Gut, 47(2), 268–271.PubMedCrossRef

Tamaki, M., Goi, T., Hirono, Y., Katayama, K., & Yamaguchi, A. (2004). Ppp2r1b gene alterations inhibit interaction of PP2A Abeta and PP2A C proteins in colorectal cancers. Oncology Reports, 11(3), 655–659.PubMed

Wang, S. S., Esplin, E. D., Li, J. L., Huang, L., Gazdar, A., Minna, J., et al. (1998). Alterations of the PPP2r1B gene in human lung and colon cancer. Science, 282(5387), 284–287.PubMedCrossRef

10.

Ruediger, R., Pham, H. T., & Walter, G. (2001). Alterations in protein phosphatase 2A subunit interaction in human carcinomas of the lung and colon with mutations in the a beta subunit gene. Oncogene, 20(15), 1892–1899.PubMedCrossRef

11.

Ruediger, R., Pham, H. T., & Walter, G. (2001). Disruption of protein phosphatase 2A subunit interaction in human cancers with mutations in the Aalpha subunit gene. Oncogene, 20(1), 10–15.PubMedCrossRef

12.

Sweet, B. H., & Hilleman, M. R. (1960). The vacuolating virus, SV40. Proceedings of the Society for Experimental Biology and Medicine, 105, 420–427.PubMed

13.

Eddy, B. E., Borman, G. S., Berkeley, W. H., & Young, R. D. (1961). Tumors induced in hamsters by injection of rhesus monkey kidney cell extracts. Proceedings of the Society for Experimental Biology and Medicine, 107, 191–197.PubMed

14.

Eddy, B. E., Borman, G. S., Grubbs, G. E., & Young, R. D. (1962). Identification of the oncogenic substance in rhesus monkey kidney cell culture as simian virus 40. Virology, 17, 65–75.PubMedCrossRef

15.

Shein, H. M., & Enders, J. F. (1962). Transformation induced by simian virus 40 in human renal cell cultures. I. Morphology and growth characteristics. Proceedings of the National Academy of Sciences of the United States of America, 48, 1164–1172.PubMedCrossRef

16.

Rabson, A. S., O’conor, G. T., Kirschstein, R. L., & Branigan, W. J. (1962). Papillary ependymomas produced in Rattus (mastomys) natalensis inoculated with vacuolating virus (SV40). Journal of National Cancer Institute, 29, 765–787.

17.

Rundell, K., & Parakati, R. (2001). The role of the SV40 ST antigen in cell growth promotion and transformation. Seminars in Cancer Biology, 11(1), 5–13.PubMedCrossRef

18.

Sullivan, C. S., & Pipas, J. M. (2002). T antigens of simian virus 40: Molecular chaperones for viral replication and tumorigenesis. Microbiology and Molecular Biology Reviews, 66(2), 179–202.PubMedCrossRef

19.

Hirakawa, T., & Ruley, H. E. (1988). Rescue of cells from ras oncogene-induced growth arrest by a second, complementing, oncogene. Proceedings of the National Academy of Sciences of the United States of America, 85(5), 1519–1523.PubMedCrossRef

20.

Michalovitz, D., Fischer-Fantuzzi, L., Vesco, C., Pipas, J. M., & Oren, M. (1987). Activated ha-ras can cooperate with defective simian virus 40 in the transformation of nonestablished rat embryo fibroblasts. Journal of Virology, 61(8), 2648–2654.PubMed

21.

Sager, R., Tanaka, K., Lau, C. C., Ebina, Y., & Anisowicz, A. (1983). Resistance of human cells to tumorigenesis induced by cloned transforming genes. Proceedings of the National Academy of Sciences of the United States of America, 80(24), 7601–7605.PubMedCrossRef

22.

Chang, L. S., Pan, S., Pater, M. M., & Di Mayorca, G. (1985). Differential requirement for SV40 early genes in immortalization and transformation of primary rat and human embryonic cells. Virology, 146(2), 246–261.PubMedCrossRef

23.

Lustig, A. J. (1999). Crisis intervention: The role of telomerase. Proceedings of the National Academy of Sciences of the United States of America, 96(7), 3339–3341.PubMedCrossRef

24.

Rangarajan, A., Hong, S. J., Gifford, A., & Weinberg, R. A. (2004). Species- and cell type-specific requirements for cellular transformation. Cancer Cells, 6(2), 171–183.CrossRef

25.

Voorhoeve, P. M., & Agami, R. (2003). The tumor-suppressive functions of the human ink4a locus. Cancer Cells, 4(4), 311–319.CrossRef

26.

Mungre, S., Enderle, K., Turk, B., Porras, A., Wu, Y. Q., Mumby, M. C., et al. (1994). Mutations which affect the inhibition of protein phosphatase 2A by simian virus 40 small-t antigen in vitro decrease viral transformation. Journal of Virology, 68(3), 1675–1681.PubMed

27.

Porras, A., Bennett, J., Howe, A., Tokos, K., Bouck, N., Henglein, B., et al. (1996). A novel simian virus 40 early-region domain mediates transactivation of the cyclin a promoter by small-t antigen and is required for transformation in small-t antigen-dependent assays. Journal of Virology, 70(10), 6902–6908.PubMed

28.

Janssens, V., & Goris, J. (2001). Protein phosphatase 2A: A highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochemistry Journal, 353(Pt 3), 417–439.CrossRef

29.

Arino, J., Woon, C. W., Brautigan, D. L., Miller Jr., T. B., & Johnson, G. L. (1988). Human liver phosphatase 2A: cDNA and amino acid sequence of two catalytic subunit isotypes. Proceedings of the National Academy of Sciences of the United States of America, 85(12), 4252–4256.PubMedCrossRef

30.

Cohen, P. (1989). The structure and regulation of protein phosphatases. Annual Reviews of Biochemistry, 58, 453–508.CrossRef

31.

Gotz, J., Probst, A., Mistl, C., Nitsch, R. M., & Ehler, E. (2000). Distinct role of protein phosphatase 2A subunit calpha in the regulation of E-cadherin and beta-catenin during development. Mechanisms of Development, 93(1–2), 83–93.PubMedCrossRef

32.

Hemmings, B. A., Adams-Pearson, C., Maurer, F., Muller, P., Goris, J., Merlevede, W., et al. (1990). Alpha- and beta-forms of the 65-kda subunit of protein phosphatase 2A have a similar 39 amino acid repeating structure. Biochemistry, 29(13), 3166–3173.PubMedCrossRef

33.

Zhou, J., Pham, H. T., Ruediger, R., & Walter, G. (2003). Characterization of the Aalpha and Abeta subunit isoforms of protein phosphatase 2A: Differences in expression, subunit interaction, and evolution. Biochemical Journal, 369(Pt 2), 387–398.PubMedCrossRef

34.

Cho, U. S., & Xu, W. (2007). Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme. Nature, 445(7123), 53–57.PubMedCrossRef

35.

Xu, Y., Xing, Y., Chen, Y., Chao, Y., Lin, Z., Fan, E., et al. (2006). Structure of the protein phosphatase 2A holoenzyme. Cell, 127(6), 1239–1251.PubMedCrossRef

36.

Mayer, R. E., Hendrix, P., Cron, P., Matthies, R., Stone, S. R., Goris, J., et al. (1991). Structure of the 55-kda regulatory subunit of protein phosphatase 2A: Evidence for a neuronal-specific isoform. Biochemistry, 30(15), 3589–3597.PubMedCrossRef

37.

Strack, S., Chang, D., Zaucha, J. A., Colbran, R. J., & Wadzinski, B. E. (1999). Cloning and characterization of b delta, a novel regulatory subunit of protein phosphatase 2A. FEBS Letters, 460(3), 462–466.PubMedCrossRef

38.

Zolnierowicz, S., Csortos, C., Bondor, J., Verin, A., Mumby, M. C., & Depaoli-Roach, A. A. (1994). Diversity in the regulatory b-subunits of protein phosphatase 2A: Identification of a novel isoform highly expressed in brain. Biochemistry, 33(39), 11858–11867.PubMedCrossRef

39.

Csortos, C., Zolnierowicz, S., Bako, E., Durbin, S. D., & Depaoli-Roach, A. A. (1996). High complexity in the expression of the B′ subunit of protein phosphatase 2A. Evidence for the existence of at least seven novel isoforms. Journal of Biological Chemistry, 271(5), 2578–2588.PubMedCrossRef

40.

Mccright, B., & Virshup, D. M. (1995). Identification of a new family of protein phosphatase 2A regulatory subunits. Journal of Biological Chemistry, 270(44), 26123–26128.PubMedCrossRef

41.

Tehrani, M. A., Mumby, M. C., & Kamibayashi, C. (1996). Identification of a novel protein phosphatase 2A regulatory subunit highly expressed in muscle. Journal of Biological Chemistry, 271(9), 5164–5170.PubMedCrossRef

42.

Hendrix, P., Mayer-Jackel, R. E., Cron, P., Goris, J., Hofsteenge, J., Merlevede, W., et al. (1993). Structure and expression of a 72-kda regulatory subunit of protein phosphatase 2A. Evidence for different size forms produced by alternative splicing. Journal of Biological Chemistry, 268(20), 15267–15276.PubMed

43.

Seger, Y. R., Garcia-Cao, M., Piccinin, S., Cunsolo, C. L., Doglioni, C., Blasco, M. A., et al. (2002). Transformation of normal human cells in the absence of telomerase activation. Cancer Cells, 2(5), 401–413.CrossRef

44.

Stevens, I., Janssens, V., Martens, E., Dilworth, S., Goris, J., & Van Hoof, C. (2003). Identification and characterization of B″-subunits of protein phosphatase 2A in Xenopus laevis oocytes and adult tissues. European Journal of Biochemistry, 270(2), 376–387.PubMedCrossRef

45.

Yan, Z., Fedorov, S. A., Mumby, M. C., & Williams, R. S. (2000). Pr48, a novel regulatory subunit of protein phosphatase 2A, interacts with cdc6 and modulates DNA replication in human cells. Molecular and Cellular Biology, 20(3), 1021–1029.PubMedCrossRef

46.

Moreno, C. S., Ramachandran, S., Ashby, D. G., Laycock, N., Plattner, C. A., Chen, W., et al. (2004). Signaling and transcriptional changes critical for transformation of human cells by simian virus 40 small tumor antigen or protein phosphatase 2A B56gamma knockdown. Cancer Research, 64(19), 6978–6988.PubMedCrossRef

47.

Mccright, B., Brothman, A. R., & Virshup, D. M. (1996). Assignment of human protein phosphatase 2A regulatory subunit genes B56alpha, B56beta, B56gamma, B56delta, and B56epsilon (PPP2r5A–PPP2r5E), highly expressed in muscle and brain, to chromosome regions 1q41, 11q12, 3p21, 6p21.1, and 7p11.2 → p12. Genomics, 36(1), 168–170.PubMedCrossRef

48.

Millward, T. A., Zolnierowicz, S., & Hemmings, B. A. (1999). Regulation of protein kinase cascades by protein phosphatase 2A. Trends in Biochemical Sciences, 24(5), 186–191.PubMedCrossRef

49.

Kong, M., Fox, C. J., Mu, J., Solt, L., Xu, A., Cinalli, R. M., et al. (2004). The PP2A-associated protein alpha4 is an essential inhibitor of apoptosis. Science, 306(5696), 695–698.PubMedCrossRef

50.

Chao, Y., Xing, Y., Chen, Y., Xu, Y., Lin, Z., Li, Z., et al. (2006). Structure and mechanism of the phosphotyrosyl phosphatase activator. Molecular Cell, 23(4), 535–546.PubMedCrossRef

51.

Leulliot, N., Vicentini, G., Jordens, J., Quevillon-Cheruel, S., Schiltz, M., Barford, D., et al. (2006). Crystal structure of the PP2A phosphatase activator: Implications for its PP2A-specific PPiase activity. Molecular Cell, 23(3), 413–424.PubMedCrossRef

52.

Chen, Y., Xu, Y., Bao, Q., Xing, Y., Li, Z., Lin, Z., et al. (2007). Structural and biochemical insights into the regulation of protein phosphatase 2A by small t antigen of SV40. Nature Structural & Molecular Biology, 14(6), 527–534.CrossRef

53.

Cho, U. S., Morrone, S., Sablina, A. A., Arroyo, J. D., Hahn, W. C., & Xu, W. (2007). Structural basis of PP2A inhibition by small t antigen. PLoS Biology, 5(8), e202.PubMedCrossRef

54.

Kamibayashi, C., Estes, R., Lickteig, R. L., Yang, S. I., Craft, C., & Mumby, M. C. (1994). Comparison of heterotrimeric protein phosphatase 2A containing different b subunits. Journal of Biological Chemistry, 269(31), 20139–20148.PubMed

55.

Chen, W., Possemato, R., Campbell, K. T., Plattner, C. A., Pallas, D. C., & Hahn, W. C. (2004). Identification of specific PP2A complexes involved in human cell transformation. Cancer Cells, 5(2), 127–136.CrossRef

56.

Sontag, E., Fedorov, S., Kamibayashi, C., Robbins, D., Cobb, M., & Mumby, M. (1993). The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation. Cell, 75(5), 887–897.PubMedCrossRef

57.

Sontag, E., Sontag, J. M., & Garcia, A. (1997). Protein phosphatase 2A is a critical regulator of protein kinase c zeta signaling targeted by SV40 small t to promote cell growth and nf-kappab activation. EMBO Journal, 16(18), 5662–5671.PubMedCrossRef

58.

Nunbhakdi-Craig, V., Craig, L., Machleidt, T., & Sontag, E. (2003). Simian virus 40 small tumor antigen induces deregulation of the actin cytoskeleton and tight junctions in kidney epithelial cells. Journal of Virology, 77(5), 2807–2818.PubMedCrossRef

59.

Howe, A. K., Gaillard, S., Bennett, J. S., & Rundell, K. (1998). Cell cycle progression in monkey cells expressing simian virus 40 small t antigen from adenovirus vectors. Journal of Virology, 72(12), 9637–9644.PubMed

60.

Dougherty, M. K., Muller, J., Ritt, D. A., Zhou, M., Zhou, X. Z., Copeland, T. D., et al. (2005). Regulation of raf-1 by direct feedback phosphorylation. Molecular Cell, 17(2), 215–224.PubMedCrossRef

61.

Frost, J. A., Alberts, A. S., Sontag, E., Guan, K., Mumby, M. C., & Feramisco, J. R. (1994). Simian virus 40 small t antigen cooperates with mitogen-activated kinases to stimulate ap-1 activity. Molecular and Cellular Biology, 14(9), 6244–6252.PubMed

62.

Ory, S., Zhou, M., Conrads, T. P., Veenstra, T. D., & Morrison, D. K. (2003). Protein phosphatase 2A positively regulates ras signaling by dephosphorylating ksr1 and raf-1 on critical 14-3-3 binding sites. Current Biology, 13(16), 1356–1364.PubMedCrossRef

63.

Alberts, A. S., Deng, T., Lin, A., Meinkoth, J. L., Schonthal, A., Mumby, M. C., et al. (1993). Protein phosphatase 2A potentates activity of promoters containing AP-1-binding elements. Molecular and Cellular Biology, 13(4), 2104–2112.PubMed

64.

Sears, R., Leone, G., Degregori, J., & Nevins, J. R. (1999). Ras enhances myc protein stability. Molecular Cell, 3(2), 169–179.PubMedCrossRef

65.

Yeh, E., Cunningham, M., Arnold, H., Chasse, D., Monteith, T., Ivaldi, G., et al. (2004). A signalling pathway controlling c-myc degradation that impacts oncogenic transformation of human cells. Nature Cell Biology, 6(4), 308–318.PubMedCrossRef

66.

Arnold, H. K., & Sears, R. C. (2006). Protein phosphatase 2A regulatory subunit B56alpha associates with c-myc and negatively regulates c-myc accumulation. Molecular and Cellular Biology, 26(7), 2832–2844.PubMedCrossRef

67.

Garcia, A., Cereghini, S., & Sontag, E. (2000). Protein phosphatase 2A and phosphatidylinositol 3-kinase regulate the activity of SP1-responsive promoters. Journal of Biological Chemistry, 275(13), 9385–9389.PubMedCrossRef

68.

Skoczylas, C., Henglein, B., & Rundell, K. (2005). PP2A-dependent transactivation of the cyclin a promoter by SV40 st is mediated by a cell cycle-regulated E2F site. Virology, 332(2), 596–601.PubMedCrossRef

69.

Watanabe, G., Howe, A., Lee, R. J., Albanese, C., Shu, I. W., Karnezis, A. N., et al. (1996). Induction of cyclin D1 by simian virus 40 small tumor antigen. Proceedings of the National Academy of Sciences of the United States of America, 93(23), 12861–12866.PubMedCrossRef

70.

Wheat, W. H., Roesler, W. J., & Klemm, D. J. (1994). Simian virus 40 small tumor antigen inhibits dephosphorylation of protein kinase a-phosphorylated CREB and regulates CREB transcriptional stimulation. Molecular and Cellular Biology, 14(9), 5881–5890.PubMed

71.

Didonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E., & Karin, M. (1997). A cytokine-responsive Ikappab kinase that activates the transcription factor NF-kappab. Nature, 388(6642), 548–554.PubMedCrossRef

72.

Zhao, J. J., Gjoerup, O. V., Subramanian, R. R., Cheng, Y., Chen, W., Roberts, T. M., et al. (2003). Human mammary epithelial cell transformation through the activation of phosphatidylinositol 3-kinase. Cancer Cells, 3(5), 483–495.CrossRef

73.

Andjelkovic, M., Jakubowicz, T., Cron, P., Ming, X. F., Han, J. W., & Hemmings, B. A. (1996). Activation and phosphorylation of a pleckstrin homology domain containing protein kinase (rac-PK/PKB) promoted by serum and protein phosphatase inhibitors. Proceedings of the Society for Experimental Biology and Medicine, 93(12), 5699–5704.

74.

Yuan, H., Veldman, T., Rundell, K., & Schlegel, R. (2002). Simian virus 40 small tumor antigen activates akt and telomerase and induces anchorage-independent growth of human epithelial cells. Journal of Virology, 76(21), 10685–10691.PubMedCrossRef

75.

Ballou, L. M., Jiang, Y. P., Du, G., Frohman, M. A., & Lin, R. Z. (2003). Ca(2+)- and phospholipase D-dependent and -independent pathways activate mTOR signaling. FEBS Letters, 550(1–3), 51–56.PubMedCrossRef

76.

Westphal, R. S., Coffee Jr., R. L., Marotta, A., Pelech, S. L., & Wadzinski, B. E. (1999). Identification of kinase-phosphatase signaling modules composed of p70 S6 kinase-protein phosphatase 2A (PP2A) and p21-activated kinase-PP2A. Journal of Biological Chemistry, 274(2), 687–692.PubMedCrossRef

77.

Sontag, J. M., & Sontag, E. (2006). Regulation of cell adhesion by PP2A and SV40 small tumor antigen: An important link to cell transformation. Cellular and Molecular Life Science, 63(24), 2979–2991.CrossRef

78.

Graessmann, A., Graessmann, M., Tjian, R., & Topp, W. C. (1980). Simian virus 40 small-t protein is required for loss of actin cable networks in rat cells. Journal of Virology, 33(3), 1182–1191.PubMed

79.

Suzuki, K., Chikamatsu, Y., & Takahashi, K. (2005). Requirement of protein phosphatase 2A for recruitment of IQGAP1 to rac-bound beta1 integrin. Journal of Cell Physiology, 203(3), 487–492.CrossRef

80.

Colella, S., Ohgaki, H., Ruediger, R., Yang, F., Nakamura, M., Fujisawa, H., et al. (2001). Reduced expression of the Aalpha subunit of protein phosphatase 2A in human gliomas in the absence of mutations in the Aalpha and Abeta subunit genes. International Journal of Cancer, 93(6), 798–804.CrossRef

81.

Suzuki, K., & Takahashi, K. (2003). Reduced expression of the regulatory a subunit of serine/threonine protein phosphatase 2A in human breast cancer MCF-7 cells. International Journal of Oncology, 23(5), 1263–1268.PubMed

82.

Chen, W., Arroyo, J. D., Timmons, J. C., Possemato, R., & Hahn, W. C. (2005). Cancer-associated PP2A Aalpha subunits induce functional haploinsufficiency and tumorigenicity. Cancer Research, 65(18), 8183–8192.PubMedCrossRef

83.

Sablina, A. A., Chen, W., Arroyo, J. D., Corral, L., Hector, M., Bulmer, S. E., et al. (2007). The tumor suppressor PP2A Abeta regulates the RalA GTPase. Cell, 129(5), 969–982.PubMedCrossRef

84.

Li, X., Scuderi, A., Letsou, A., & Virshup, D. M. (2002). B56-associated protein phosphatase 2A is required for survival and protects from apoptosis in drosophila melanogaster. Molecular and Cellular Biology, 22(11), 3674–3684.PubMedCrossRef

85.

Strack, S., Cribbs, J. T., & Gomez, L. (2004). Critical role for protein phosphatase 2A heterotrimers in mammalian cell survival. Journal of Biological Chemistry, 279(46), 47732–47739.PubMedCrossRef

86.

Francia, G., Mitchell, S. D., Moss, S. E., Hanby, A. M., Marshall, J. F., & Hart, I. R. (1996). Identification by differential display of annexin-vi, a gene differentially expressed during melanoma progression. Cancer Research, 56(17), 3855–3858.PubMed

87.

Deichmann, M., Polychronidis, M., Wacker, J., Thome, M., & Naher, H. (2001). The protein phosphatase 2A subunit B56gamma gene is identified to be differentially expressed in malignant melanomas by subtractive suppression hybridization. Melanoma Research, 11(6), 577–585.PubMedCrossRef

88.

Polakis, P. (2000). Wnt signaling and cancer. Genes and Development, 14(15), 1837–1851.PubMed

89.

Li, H. H., Cai, X., Shouse, G. P., Piluso, L. G., & Liu, X. (2007). A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. EMBO Journal, 26(2), 402–411.PubMedCrossRef

90.

Okamoto, K., Li, H., Jensen, M. R., Zhang, T., Taya, Y., Thorgeirsson, S. S., & Prives, C. (2002). Cyclin g recruits PP2A to dephosphorylate Mdm2. Molecular Cell, 9(4), 761–771.PubMedCrossRef

91.

Wei, W., Jobling, W. A., Chen, W., Hahn, W. C., & Sedivy, J. M. (2003). Abolition of cyclin-dependent kinase inhibitor p16ink4a and p21cip1/waf1 functions permits ras-induced anchorage-independent growth in telomerase-immortalized human fibroblasts. Molecular and Cellular Biology, 23(8), 2859–2870.PubMedCrossRef

92.

Camonis, J. H., & White, M. A. (2005). Ral GTPases: Corrupting the exocyst in cancer cells. Trends in Cell Biology, 15(6), 327–332.PubMedCrossRef

93.

Feig, L. A. (2003). Ral-GTPases: Approaching their 15 minutes of fame. Trends in Cell Biology, 13(8), 419–425.PubMedCrossRef

94.

Feinstein, E. (2005). Ral-GTPases: Good chances for a long-lasting fame. Oncogene, 24(3), 326–328.PubMedCrossRef

95.

Goi, T., Shipitsin, M., Lu, Z., Foster, D. A., Klinz, S. G., & Feig, L. A. (2000). An egf receptor/ral-GTPase signaling cascade regulates c-src activity and substrate specificity. EMBO Journal, 19(4), 623–630.PubMedCrossRef

96.

Jiang, H., Luo, J. Q., Urano, T., Frankel, P., Lu, Z., Foster, D. A., & Feig, L. A. (1995). Involvement of ral GTPase in v-src-induced phospholipase D activation. Nature, 378(6555), 409–412.PubMedCrossRef

97.

Moskalenko, S., Henry, D. O., Rosse, C., Mirey, G., Camonis, J. H., & White, M. A. (2002). The exocyst is a ral effector complex. Nature Cell Biology, 4(1), 66–72.PubMedCrossRef

98.

Adler, H. T., Nallaseth, F. S., Walter, G., & Tkachuk, D. C. (1997). Hrx leukemic fusion proteins form a heterocomplex with the leukemia-associated protein SET and protein phosphatase 2A. Journal of Biological Chemistry, 272(45), 28407–28414.PubMedCrossRef

99.

Gildea, J. J., Harding, M. A., Seraj, M. J., Gulding, K. M., & Theodorescu, D. (2002). The role of RalA in epidermal growth factor receptor-regulated cell motility. Cancer Research, 62(4), 982–985.PubMed

100.

Ohta, Y., Suzuki, N., Nakamura, S., Hartwig, J. H., & Stossel, T. P. (1999). The small GTPase RalA targets filamin to induce filopodia. Proceedings of the Society for Experimental Biology and Medicine, 96(5), 2122–2128.

101.

Tchevkina, E., Agapova, L., Dyakova, N., Martinjuk, A., Komelkov, A., & Tatosyan, A. (2005). The small G-protein RalA stimulates metastasis of transformed cells. Oncogene, 24(3), 329–335.PubMedCrossRef

102.

Chien, Y., & White, M. A. (2003). Ral GTPases are linchpin modulators of human tumor-cell proliferation and survival. EMBO Reports, 4(8), 800–806.PubMedCrossRef

103.

Lim, K. H., Baines, A. T., Fiordalisi, J. J., Shipitsin, M., Feig, L. A., Cox, A. D., et al. (2005). Activation of RalA is critical for ras-induced tumorigenesis of human cells. Cancer Cells, 7(6), 533–545.CrossRef

104.

Panner, A., Nakamura, J. L., Parsa, A. T., Rodriguez-Viciana, P., Berger, M. S., Stokoe, D., et al. (2006). mTOR-independent translational control of the extrinsic cell death pathway by RalA. Molecular and Cellular Biology, 26(20), 7345–7357.PubMedCrossRef

105.

Li, M., Makkinje, A., & Damuni, Z. (1996). The myeloid leukemia-associated protein set is a potent inhibitor of protein phosphatase 2A. Journal of Biological Chemistry, 271(19), 11059–11062.PubMedCrossRef

106.

Seo, S. B., Mcnamara, P., Heo, S., Turner, A., Lane, W. S., & Chakravarti, D. (2001). Regulation of histone acetylation and transcription by INHAT, a human cellular complex containing the SET oncoprotein. Cell, 104(1), 119–130.PubMedCrossRef

107.

Canela, N., Rodriguez-Vilarrupla, A., Estanyol, J. M., Diaz, C., Pujol, M. J., Agell, N., et al. (2003). The set protein regulates G2/M transition by modulating cyclin B-cyclin-dependent kinase 1 activity. Journal of Biological Chemistry, 278(2), 1158–1164.PubMedCrossRef

108.

Kumar, R. N., Radhakrishnan, R., Ha, J. H., & Dhanasekaran, N. (2004). Proteome analysis of NIH3T3 cells transformed by activated Galpha12: Regulation of leukemia-associated protein set. Journal of Proteome Research, 3(6), 1177–1183.PubMedCrossRef

109.

Carlson, S. G., Eng, E., Kim, E. G., Perlman, E. J., Copeland, T. D., & Ballermann, B. J. (1998). Expression of set, an inhibitor of protein phosphatase 2A, in renal development and Wilms’ tumor. Journal of the American Society of Nephrology, 9(10), 1873–1880.PubMed

110.

Fornerod, M., Boer, J., Van Baal, S., Jaegle, M., Von Lindern, M., Murti, K. G., et al. (1995). Relocation of the carboxyterminal part of CAN from the nuclear envelope to the nucleus as a result of leukemia-specific chromosome rearrangements. Oncogene, 10(9), 1739–1748.PubMed

111.

Von Lindern, M., Van Baal, S., Wiegant, J., Raap, A., Hagemeijer, A., & Grosveld, G. (1992). 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, 12(8), 3346–3355.

112.

Fan, Z., Beresford, P. J., Oh, D. Y., Zhang, D., & Lieberman, J. (2003). Tumor suppressor NM23-H1 is a granzyme A-activated DNAase during CTL-mediated apoptosis, and the nucleosome assembly protein set is its inhibitor. Cell, 112(5), 659–672.PubMedCrossRef

113.

Junttila, M. R., Puustinen, P., Niemela, M., Ahola, R., Arnold, H., Bottzauw, T., et al. (2007). CIP2A inhibits PP2A in human malignancies. Cell, 130(1), 51–62.PubMedCrossRef

Title: SV40 small T antigen and PP2A phosphatase in cell transformation
Authors: Anna A. Sablina
William C. Hahn
Publication date: 01-06-2008
Publisher: Springer US
Published in: Cancer and Metastasis Reviews / Issue 2/2008
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-008-9116-0

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The STEP trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 2/2008

A tumor suppressor role for PP2A-B56α through negative regulation of c-Myc and other key oncoproteins

Protein tyrosine phosphatase epsilon and Neu-induced mammary tumorigenesis

The role of serine/threonine protein phosphatase type 5 (PP5) in the regulation of stress-induced signaling networks and cancer

Demethylation of (Cytosine-5-C-methyl) DNA and regulation of transcription in the epigenetic pathways of cancer development

MT4-(MMP17) and MT6-MMP (MMP25), A unique set of membrane-anchored matrix metalloproteinases: properties and expression in cancer

Protein phosphatase 2A (PP2A), a drugable tumor suppressor in Ph1(+) leukemias

Keynote webinar | Spotlight on antibody–drug conjugates in cancer