Response to DNA damage: Why do we need to focus on protein phosphatases?

Frontiers in Oncology

Volumn 3 JAN, Issue , 2013, Pages

  Shimada, Midori ^a   Nakanishi, Makoto ^a  

^a NAGOYA CITY UNIVERSITY GRADUATE SCHOOL OF MEDICAL SCIENCES   (Japan)

Author keywords

Chromatin; DNA damage response; DNA repair; Phosphorylation; Protein phosphatase

Indexed keywords

ATM PROTEIN; BRCA1 ASSOCIATED PROTEIN REQUIRED FOR ATM ACTIVATION 1 PROTEIN; BRCA1 PROTEIN; CHECKPOINT KINASE 1; CHECKPOINT KINASE 2; DNA DEPENDENT PROTEIN KINASE; HISTONE H2AX; HISTONE H3; KAP1 PROTEIN; KU ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHOPROTEIN PHOSPHATASE; PHOSPHOPROTEIN PHOSPHATASE 1; PHOSPHOPROTEIN PHOSPHATASE 2A; PHOSPHOPROTEIN PHOSPHATASE 2C; PHOSPHOPROTEIN PHOSPHATASE 4; PHOSPHOPROTEIN PHOSPHATASE 5; PHOSPHOPROTEIN PHOSPHATASE 6; PROTEIN MDM2; PROTEIN P16; PROTEIN P19; PROTEIN P53; PROTEIN PHOSPHATASE PPM1G; PROTEIN SERINE THREONINE KINASE; RAD51 PROTEIN; REPLICATION FACTOR C; RETINOBLASTOMA PROTEIN; RPA2 PROTEIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; WIP1 PHOSPHATASE;

APOPTOSIS; ARTICLE; CANCER THERAPY; CELL CYCLE PROGRESSION; CELL CYCLE REGULATION; DNA DAMAGE; DNA REPAIR; G2 PHASE CELL CYCLE CHECKPOINT; HUMAN; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN SUBUNIT; UBIQUITINATION; ULTRAVIOLET IRRADIATION;

EID: 84875879746     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2013.00008     Document Type: Article

References (173)

1. Aglipay, J. A., Martin, S. A., Tawara, H., Lee, S. W., and Ouchi, T. (2006). ATM activation by ionizing radiation requires BRCA1-associated BAAT1. J. Biol. Chem. 281, 9710-9718.
2. Ahn, J. Y., Schwarz, J. K., Piwnica-Worms, H., and Canman, C. E. (2000). Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res. 60, 5934-5936.
3. Alberts, A. S., Thorburn, A. M., Shenolikar, S., Mumby, M. C., and Feramisco, J. R. (1993). Regulation of cell cycle progression and nuclear affinity of the retinoblastoma protein by protein phosphatases. Proc. Natl. Acad. Sci. U.S.A. 90, 388-392.
4. Ali, A., Zhang, J., Bao, S., Liu, I., Otterness, D., Dean, N. M., et al. (2004). Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation. Genes Dev. 18, 249-254.
5. Allemand, E., Hastings, M. L., Murray, M. V., Myers, M. P., and Krainer, A. R. (2007). Alternative splicing regulation by interaction of phosphatase PP2Cgamma with nucleic acid-binding protein YB-1. Nat. Struct. Mol. Biol. 14, 630-638.
6. Amable, L., Grankvist, N., Largen, J. W., Ortsater, H., Sjoholm, A., and Honkanen, R. E. (2011). Disruption of serine/threonine protein phosphatase 5 (PP5, PPP5c) in mice reveals a novel role for PP5 in the regulation of ultraviolet light-induced phosphorylation of serine/threonine protein kinase Chk1 (CHEK1). J. Biol. Chem. 286, 40413-40422.
7. Anantha, R. W., Vassin, V. M., and Borowiec, J. A. (2007). Sequential and synergistic modification of human RPA stimulates chromosomal DNA repair. J. Biol. Chem. 282, 35910-35923.
8. Andreassen, P. R., Lacroix, F. B., Villa-Moruzzi, E., and Margolis, R. L. (1998). Differential subcellular localization of protein phosphatase-1 alpha, gamma1, and delta isoforms during both interphase and mitosis in mammalian cells. J. Cell Biol. 141, 1207-1215.
9. Appella, E., and Anderson, C. W. (2001). Post-translational modifications and activation of p53 by genotoxic stresses. Eur. J. Biochem. 268, 2764-2772.
10. Avni, D., Yang, H., Martelli, F., Hofmann, F., ElShamy, W. M., Ganesan, S., et al. (2003). Active localization of the retinoblastoma protein in chromatin and its response to S phase DNA damage. Mol. Cell 12, 735-746.
11. Bakkenist, C. J., and Kastan, M. B. (2003). DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421, 499-506.
12. Bartek, J., and Lukas, J. (2003). Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell 3, 421-429.
13. Bennetzen, M. V., Larsen, D. H., Bunkenborg, J., Bartek, J., Lukas, J., and Andersen, J. S. (2010). Site-specific phosphorylation dynamics of the nuclear proteome during the DNA damage response. Mol. Cell. Proteomics 9, 1314-1323.
14. Bensimon, A., Schmidt, A., Ziv, Y., Elkon, R., Wang, S. Y., Chen, D. J., et al. (2010). ATM-dependent and -independent dynamics of the nuclear phosphoproteome after DNA damage. Sci. Signal. 3, rs3.
15. Bermudez, V. P., Lindsey-Boltz, L. A., Cesare, A. J., Maniwa, Y., Griffith, J. D., Hurwitz, J., et al. (2003). Loading of the human 9-1-1 checkpoint complex onto DNA by the checkpoint clamp loader hRad17-replication factor C complex in vitro. Proc. Natl. Acad. Sci. U.S.A. 100, 1633-1638.
16. Berndt, N., Dohadwala, M., and Liu, C. W. (1997). Constitutively active protein phosphatase 1alpha causes Rb-dependent G1 arrest in human cancer cells. Curr. Biol. 7, 375-386.
17. Block, W. D., Yu, Y., Merkle, D., Gifford, J. L., Ding, Q., Meek, K., et al. (2004). Autophosphorylation-dependent remodeling of the DNA-dependent protein kinase catalytic subunit regulates ligation of DNA ends. Nucleic Acids Res. 32, 4351-4357.
18. Brewis, N. D., Street, A. J., Prescott, A. R., and Cohen, P. T. (1993). PPX, a novel protein serine/threonine phosphatase localized to centrosomes. EMBO J. 12, 987-996.
19. Bulavin, D. V., Demidov, O. N., Saito, S., Kauraniemi, P., Phillips, C., Amundson, S. A., et al. (2002). Amplification of PPM1D in human tumors abrogates p53 tumor-suppressor activity. Nat. Genet. 31, 210-215.
20. Bulavin, D. V., Phillips, C., Nannenga, B., Timofeev, O., Donehower, L. A., Anderson, C. W., et al. (2004). Inactivation of the Wip1 phosphatase inhibits mammary tumorigenesis through p38 MAPK-mediated activation of the p16(Ink4a)-p19(Arf) pathway. Nat. Genet. 36, 343-350.
21. Bulavin, D. V., Saito, S., Hollander, M. C., Sakaguchi, K., Anderson, C. W., Appella, E., et al. (1999). Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J. 18, 6845-6854.
22. Burma, S., Chen, B. P., Murphy, M., Kurimasa, A., and Chen, D. J. (2001). ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J. Biol. Chem. 276, 42462-42467.
23. Cha, H., Lowe, J. M., Li, H., Lee, J. S., Belova, G. I., Bulavin, D. V., et al. (2010). Wip1 directly dephosphorylates gamma-H2AX and attenuates the DNA damage response. Cancer Res. 70, 4112-4122.
24. Chan, D. W., Chen, B. P., Prithivirajsingh, S., Kurimasa, A., Story, M. D., Qin, J., et al. (2002). Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev. 16, 2333-2338.
25. Chen, B. P., Chan, D. W., Kobayashi, J., Burma, S., Asaithamby, A., Morotomi-Yano, K., et al. (2005). Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks. J. Biol. Chem. 280, 14709-14715.
26. Chen, G. I., Tisayakorn, S., Jorgensen, C., D'Ambrosio, L. M., Goudreault, M., and Gingras, A. C. (2008). PP4R4/KIAA1622 forms a novel stable cytosolic complex with phosphoprotein phosphatase 4. J. Biol. Chem. 283, 29273-29284.
27. Chen, M. S., Silverstein, A. M., Pratt, W. B., and Chinkers, M. (1996). The tetratricopeptide repeat domain of protein phosphatase 5 mediates binding to glucocorticoid receptor heterocomplexes and acts as a dominant negative mutant. J. Biol. Chem. 271, 32315-32320.
28. Chinkers, M. (2001). Protein phosphatase 5 in signal transduction. Trends Endocrinol. Metab. 12, 28-32.
29. Choi, J., Nannenga, B., Demidov, O. N., Bulavin, D. V., Cooney, A., Brayton, C., et al. (2002). Mice deficient for the wild-type p53-induced phosphatase gene (Wip1) exhibit defects in reproductive organs, immune function, and cell cycle control. Mol. Cell. Biol. 22, 1094-1105.
30. Chou, D. M., Petersen, P., Walter, J. C., and Walter, G. (2002). Protein phosphatase 2A regulates binding of Cdc45 to the prereplication complex. J. Biol. Chem. 277, 40520-40527.
31. Chowdhury, D., Keogh, M. C., Ishii, H., Peterson, C. L., Buratowski, S., and Lieberman, J. (2005). γ-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol. Cell 20, 801-809.
32. Chowdhury, D., Xu, X., Zhong, X., Ahmed, F., Zhong, J., Liao, J., et al. (2008). A PP4-phosphatase complex dephosphorylates gamma-H2AX generated during DNA replication. Mol. Cell 31, 33-46.
33. Cicchillitti, L., Fasanaro, P., Biglioli, P., Capogrossi, M. C., and Martelli, F. (2003). Oxidative stress induces protein phosphatase 2A-dependent dephosphorylation of the pocket proteins pRb, p107, and p130. J. Biol. Chem. 278, 19509-19517.
34. Clarke, C. A., and Clarke, P. R. (2005). DNA-dependent phosphorylation of Chk1 and Claspin in a human cell-free system. Biochem. J. 388, 705-712.
35. Cohen, P. T. (2002). Protein phosphatase 1 - targeted in many directions. J. Cell Sci. 115, 241-256.
36. Cohen, P. T., Philp, A., and Vazquez-Martin, C. (2005). Protein phosphatase 4 - from obscurity to vital functions. FEBS Lett. 579, 3278-3286.
37. Cortez, D., Wang, Y., Qin, J., and Elledge, S. J. (1999). Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 286, 1162-1166.
38. Cui, X., Yu, Y., Gupta, S., Cho, Y. M., Lees-Miller, S. P., and Meek, K. (2005). Autophosphorylation of DNA-dependent protein kinase regulates DNA end processing and may also alter double-strand break repair pathway choice. Mol. Cell. Biol. 25, 10842-10852.
39. Daniel, J. A., Pellegrini, M., Lee, J. H., Paull, T. T., Feigenbaum, L., and Nussenzweig, A. (2008). Multiple autophosphorylation sites are dispensable for murine ATM activation in vivo. J. Cell Biol. 183, 777-783.
40. Darlington, Y., Nguyen, T. A., Moon, S. H., Herron, A., Rao, P., Zhu, C., et al. (2012). Absence of Wip1 partially rescues Atm deficiency phenotypes in mice. Oncogene 31, 1155-1165.
41. De Leon, G., Sherry, T. C., and Krucher, N. A. (2008). Reduced expression of PNUTS leads to activation of Rb-phosphatase and caspase-mediated apoptosis. Cancer Biol. Ther. 7, 833-841.
42. Delacroix, S., Wagner, J. M., Kobayashi, M., Yamamoto, K., and Karnitz, L. M. (2007). The Rad9-Hus1-Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev. 21, 1472-1477.
43. den Elzen, N. R., and O'Connell, M. J. (2004). Recovery from DNA damage checkpoint arrest by PP1-mediated inhibition of Chk1. EMBO J. 23, 908-918.
44. Ding, Q., Reddy, Y. V., Wang, W., Woods, T., Douglas, P., Ramsden, D. A., et al. (2003). Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair. Mol. Cell. Biol. 23, 5836-5848.
45. Dohadwala, M., da Cruz e Silva, E. F., Hall, F. L., Williams, R. T., Carbonaro-Hall, D. A., Nairn, A. C., et al. (1994). Phosphorylation and inactivation of protein phosphatase 1 by cyclin-dependent kinases. Proc. Natl. Acad. Sci. U.S.A. 91, 6408-6412.
46. Dohoney, K. M., Guillerm, C., Whiteford, C., Elbi, C., Lambert, P. F., Hager, G. L., et al. (2004). Phosphorylation of p53 at serine 37 is important for transcriptional activity and regulation in response to DNA damage. Oncogene 23, 49-57.
47. Douglas, P., Moorhead, G. B., Ye, R., and Lees-Miller, S. P. (2001). Protein phosphatases regulate DNA-dependent protein kinase activity. J. Biol. Chem. 276, 18992-18998.
48. Douglas, P., Zhong, J., Ye, R., Moorhead, G. B., Xu, X., and Lees-Miller, S. P. (2010). Protein phosphatase 6 interacts with the DNA-dependent protein kinase catalytic subunit and dephosphorylates gamma-H2AX. Mol. Cell. Biol. 30, 1368-1381.
49. Dozier, C., Bonyadi, M., Baricault, L., Tonasso, L., and Darbon, J. M. (2004). Regulation of Chk2 phosphorylation by interaction with protein phosphatase 2A via its B′ regulatory subunit. Biol. Cell 96, 509-517.
50. Dumaz, N., and Meek, D. W. (1999). Serine15 phosphorylation stimulates p53 transactivation but does not directly influence interaction with HDM2. EMBO J. 18, 7002-7010.
51. Durfee, T., Becherer, K., Chen, P. L., Yeh, S. H., Yang, Y., Kilburn, A. E., et al. (1993). The retinoblastoma protein associates with the protein phosphatase type 1 catalytic subunit. Genes Dev. 7, 555-569.
52. Falck, J., Coates, J., and Jackson, S. P. (2005). Conserved modes of recruitment of ATM, ATR and DNA-PKcs to sites of DNA damage. Nature 434, 605-611.
53. Falck, J., Mailand, N., Syljuasen, R. G., Bartek, J., and Lukas, J. (2001). The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 410, 842-847.
54. Feng, J., Wakeman, T., Yong, S., Wu, X., Kornbluth, S., and Wang, X. F. (2009). Protein phosphatase 2A-dependent dephosphorylation of replication protein A is required for the repair of DNA breaks induced by replication stress. Mol. Cell. Biol. 29, 5696-5709.
55. Fiscella, M., Zhang, H., Fan, S., Sakaguchi, K., Shen, S., Mercer, W. E., et al. (1997). Wip1, a novel human protein phosphatase that is induced in response to ionizing radiation in a p53-dependent manner. Proc. Natl. Acad. Sci. U.S.A. 94, 6048-6053.
56. Freeman, A. K., Dapic, V., and Monteiro, A. N. (2010). Negative regulation of CHK2 activity by protein phosphatase 2A is modulated by DNA damage. Cell Cycle 9, 736-747.
57. Fujimoto, H., Onishi, N., Kato, N., Takekawa, M., Xu, X. Z., Kosugi, A., et al. (2006). Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase. Cell Death Differ. 13, 1170-1180.
58. Garriga, J., Jayaraman, A. L., Limon, A., Jayadeva, G., Sotillo, E., Truongcao, M., et al. (2004). A dynamic equilibrium between CDKs and PP2A modulates phosphorylation of pRB, p107 and p130. Cell Cycle 3, 1320-1330.
59. Goodarzi, A. A., Jonnalagadda, J. C., Douglas, P., Young, D., Ye, R., Moorhead, G. B., et al. (2004). Autophosphorylation of ataxia-telangiectasia mutated is regulated by protein phosphatase 2A. EMBO J. 23, 4451-4461.
60. Goodarzi, A. A., Noon, A. T., Deckbar, D., Ziv, Y., Shiloh, Y., Lobrich, M., et al. (2008). ATM signaling facilitates repair of DNA double-strand breaks associated with heterochromatin. Mol. Cell 31, 167-177.
61. Gottlieb, T. M., and Jackson, S. P. (1993). The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell 72, 131-142.
62. Guo, C. Y., Brautigan, D. L., and Larner, J. M. (2002). ATM-dependent dissociation of B55 regulatory subunit from nuclear PP2A in response to ionizing radiation. J. Biol. Chem. 277, 4839-4844.
63. Hamilton, J., Grawenda, A. M., and Bernhard, E. J. (2009). Phosphatase inhibition and cell survival after DNA damage induced by radiation. Cancer Biol. Ther. 8, 1577-1586.
64. Hastie, C. J., Carnegie, G. K., Morrice, N., and Cohen, P. T. (2000). A novel 50 kDa protein forms complexes with protein phosphatase 4 and is located at centrosomal microtubule organizing centres. Biochem. J. 347, 845-855.
65. Helps, N. R., Brewis, N. D., Lineruth, K., Davis, T., Kaiser, K., and Cohen, P. T. (1998). Protein phosphatase 4 is an essential enzyme required for organisation of microtubules at centrosomes in Drosophila embryos. J. Cell Sci. 111, 1331-1340.
66. Hirao, A., Kong, Y. Y., Matsuoka, S., Wakeham, A., Ruland, J., Yoshida, H., et al. (2000). DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science 287, 1824-1827.
67. Hirasawa, A., Saito-Ohara, F., Inoue, J., Aoki, D., Susumu, N., Yokoyama, T., et al. (2003). Association of 17q21-q24 gain in ovarian clear cell adenocarcinomas with poor prognosis and identification of PPM1D and APPBP2 as likely amplification targets. Clin. Cancer Res. 9, 1995-2004.
68. Hirschi, A., Cecchini, M., Steinhardt, R. C., Schamber, M. R., Dick, F. A., and Rubin, S. M. (2010). An overlapping kinase and phosphatase docking site regulates activity of the retinoblastoma protein. Nat. Struct. Mol. Biol. 17, 1051-1057.
69. Hsu, L. C. (2007). Identification and functional characterization of a PP1-binding site in BRCA1. Biochem. Biophys. Res. Commun. 360, 507-512.
70. Huen, M. S., Sy, S. M., and Chen, J. (2010). BRCA1 and its toolbox for the maintenance of genome integrity. Nat. Rev. Mol. Cell Biol. 11, 138-148.
71. Jack, M. T., Woo, R. A., Hirao, A., Cheung, A., Mak, T. W., and Lee, P. W. (2002). Chk2 is dispensable for p53-mediated G1 arrest but is required for a latent p53-mediated apoptotic response. Proc. Natl. Acad. Sci. U.S.A. 99, 9825-9829.
72. Kang, Y., Lee, J. H., Hoan, N. N., Sohn, H. M., Chang, I. Y., and You, H. J. (2009). Protein phosphatase 5 regulates the function of 53BP1 after neocarzinostatin-induced DNA damage. J. Biol. Chem. 284, 9845-9853.
73. Katsuragi, Y., and Sagata, N. (2004). Regulation of Chk1 kinase by autoinhibition and ATR-mediated phosphorylation. Mol. Biol. Cell 15, 1680-1689.
74. Khoronenkova, S. V., Dianova, I. I., Ternette, N., Kessler, B. M., Parsons, J. L., and Dianov, G. L. (2012). ATM-dependent downregulation of USP7/HAUSP by PPM1G activates p53 response to DNA damage. Mol. Cell 45, 801-813.
75. Kimura, H., Takizawa, N., Allemand, E., Hori, T., Iborra, F. J., Nozaki, N., et al. (2006). A novel histone exchange factor, protein phosphatase 2Cgamma, mediates the exchange and dephosphorylation of H2A-H2B. J. Cell Biol. 175, 389-400.
76. Kondo, T., Wakayama, T., Naiki, T., Matsumoto, K., and Sugimoto, K. (2001). Recruitment of Mec1 and Ddc1 checkpoint proteins to double-strand breaks through distinct mechanisms. Science 294, 867-870.
77. Kozlov, S. V., Graham, M. E., Peng, C., Chen, P., Robinson, P. J., and Lavin, M. F. (2006). Involvement of novel autophosphorylation sites in ATM activation. EMBO J. 25, 3504-3514.
78. Kramer, A., Mailand, N., Lukas, C., Syljuasen, R. G., Wilkinson, C. J., Nigg, E. A., et al. (2004). Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase. Nat. Cell Biol. 6, 884-891.
79. Krucher, N. A., Rubin, E., Tedesco, V. C., Roberts, M. H., Sherry, T. C., and De Leon, G. (2006). Dephosphorylation of Rb (Thr-821) in response to cell stress. Exp. Cell Res. 312, 2757-2763.
80. Kuntziger, T., Landsverk, H. B., Collas, P., and Syljuasen, R. G. (2011). Protein phosphatase 1 regulators in DNA damage signaling. Cell Cycle 10, 1356-1362.
81. Kwon, Y. G., Lee, S. Y., Choi, Y., Greengard, P., and Nairn, A. C. (1997). Cell cycle-dependent phosphorylation of mammalian protein phosphatase 1 by cdc2 kinase. Proc. Natl. Acad. Sci. U.S.A. 94, 2168-2173.
82. Lee, D. H., Pan, Y., Kanner, S., Sung, P., Borowiec, J. A., and Chowdhury, D. (2010). A PP4 phosphatase complex dephosphorylates RPA2 to facilitate DNA repair via homologous recombination. Nat. Struct. Mol. Biol. 17, 365-372.
83. Lee, J., Kumagai, A., and Dunphy, W. G. (2007a). The Rad9-Hus1-Rad1 checkpoint clamp regulates interaction of TopBP1 with ATR. J. Biol. Chem. 282, 28036-28044.
84. Lee, S. J., Lim, C. J., Min, J. K., Lee, J. K., Kim, Y. M., Lee, J. Y., et al. (2007b). Protein phosphatase 1 nuclear targeting subunit is a hypoxia inducible gene: its role in post-translational modification of p53 and MDM2. Cell Death Differ. 14, 1106-1116.
85. Lee, J. H., and Paull, T. T. (2005). ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex. Science 308, 551-554.
86. Lee, J. S., Collins, K. M., Brown, A. L., Lee, C. H., and Chung, J. H. (2000). hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response. Nature 404, 201-204.
87. Leung-Pineda, V., Ryan, C. E., and Piwnica-Worms, H. (2006). Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit. Mol. Cell. Biol. 26, 7529-7538.
88. Li, D. W., Fass, U., Huizar, I., and Spector, A. (1998). Okadaic acid-induced lens epithelial cell apoptosis requires inhibition of phosphatase-1 and is associated with induction of gene expression including p53 and bax. Eur. J. Biochem. 257, 351-361.
89. Li, D. W., Liu, J. P., Schmid, P. C., Schlosser, R., Feng, H., Liu, W. B., et al. (2006). Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities. Oncogene 25, 3006-3022.
90. Li, H. H., Cai, X., Shouse, G. P., Piluso, L. G., and Liu, X. (2007). A specific PP2A regulatory subunit, B56gamma, mediates DNA damage-induced dephosphorylation of p53 at Thr55. EMBO J. 26, 402-411.
91. Li, H. H., Li, A. G., Sheppard, H. M., and Liu, X. (2004). Phosphorylation on Thr-55 by TAF1 mediates degradation of p53: a role for TAF1 in cell G1 progression. Mol. Cell 13, 867-878.
92. Li, J., and Stern, D. F. (2005). DNA damage regulates Chk2 association with chromatin. J. Biol. Chem. 280, 37948-37956.
93. Li, J., Yang, Y., Peng, Y., Austin, R. J., van Eyndhoven, W. G., Nguyen, K. C., et al. (2002). Oncogenic properties of PPM1D located within a breast cancer amplification epicenter at 17q23. Nat. Genet. 31, 133-134.
94. Li, X., Lin, H. H., Chen, H., Xu, X., Shih, H. M., and Ann, D. K. (2010). SUMOylation of the transcriptional co-repressor KAP1 is regulated by the serine and threonine phosphatase PP1. Sci. Signal. 3, ra32.
95. Liang, X., Reed, E., and Yu, J. J. (2006). Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells. Int. J. Mol. Med. 17, 703-708.
96. Lin, X. H., Walter, J., Scheidtmann, K., Ohst, K., Newport, J., and Walter, G. (1998). Protein phosphatase 2A is required for the initiation of chromosomal DNA replication. Proc. Natl. Acad. Sci. U.S.A. 95, 14693-14698.
97. Liu, Q., Guntuku, S., Cui, X. S., Matsuoka, S., Cortez, D., Tamai, K., et al. (2000). Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev. 14, 1448-1459.
98. Liu, Y., Virshup, D. M., White, R. L., and Hsu, L. C. (2002). Regulation of BRCA1 phosphorylation by interaction with protein phosphatase 1alpha. Cancer Res. 62, 6357-6361.
99. Loffler, H., Bochtler, T., Fritz, B., Tews, B., Ho, A. D., Lukas, J., et al. (2007). DNA damage-induced accumulation of centrosomal Chk1 contributes to its checkpoint function. Cell Cycle 6, 2541-2548.
100. Lu, J., Kovach, J. S., Johnson, F., Chiang, J., Hodes, R., Lonser, R., et al. (2009). Inhibition of serine/threonine phosphatase PP2A enhances cancer chemotherapy by blocking DNA damage induced defense mechanisms. Proc. Natl. Acad. Sci. U.S.A. 106, 11697-11702.
101. Lu, X., Bocangel, D., Nannenga, B., Yamaguchi, H., Appella, E., and Donehower, L. A. (2004). The p53-induced oncogenic phosphatase PPM1D interacts with uracil DNA glycosylase and suppresses base excision repair. Mol. Cell 15, 621-634.
102. Lu, X., Ma, O., Nguyen, T. A., Jones, S. N., Oren, M., and Donehower, L. A. (2007). The Wip1 Phosphatase acts as a gatekeeper in the p53-Mdm2 autoregulatory loop. Cancer Cell 12, 342-354.
103. Lu, X., Nannenga, B., and Donehower, L. A. (2005). PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev. 19, 1162-1174.
104. Ludlow, J. W., Glendening, C. L., Livingston, D. M., and DeCarprio, J. A. (1993). Specific enzymatic dephosphorylation of the retinoblastoma protein. Mol. Cell. Biol. 13, 367-372.
105. Magenta, A., Fasanaro, P., Romani, S., Di Stefano, V., Capogrossi, M. C., and Martelli, F. (2008). Protein phosphatase 2A subunit PR70 interacts with pRb and mediates its dephosphorylation. Mol. Cell. Biol. 28, 873-882.
106. Matsuoka, S., Ballif, B. A., Smogorzewska, A., McDonald, E. R. III, Hurov, K. E., Luo, J., et al. (2007). ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316, 1160-1166.
107. Maya, R., Balass, M., Kim, S. T., Shkedy, D., Leal, J. F., Shifman, O., et al. (2001). ATM-dependent phosphorylation of Mdm2 on serine 395, role in p53 activation by DNA damage. Genes Dev. 15, 1067-1077.
108. Melchionna, R., Chen, X. B., Blasina, A., and McGowan, C. H. (2000). Threonine 68 is required for radiation-induced phosphorylation and activation of Cds1. Nat. Cell Biol. 2, 762-765.
109. Melo, J. A., Cohen, J., and Toczyski, D. P. (2001). Two checkpoint complexes are independently recruited to sites of DNA damage in vivo. Genes Dev. 15, 2809-2821.
110. Merkle, D., Douglas, P., Moorhead, G. B., Leonenko, Z., Yu, Y., Cramb, D., et al. (2002). The DNA-dependent protein kinase interacts with DNA to form a protein-DNA complex that is disrupted by phosphorylation. Biochemistry 41, 12706-12714.
111. Mi, J., Bolesta, E., Brautigan, D. L., and Larner, J. M. (2009a). PP2A regulates ionizing radiation-induced apoptosis through Ser46 phosphorylation of p53. Mol. Cancer Ther. 8, 135-140.
112. Mi, J., Dziegielewski, J., Bolesta, E., Brautigan, D. L., and Larner, J. M. (2009b). Activation of DNA-PK by ionizing radiation is mediated by protein phosphatase 6. PLoS ONE 4:e4395. doi: 10.1371/journal.pone.0004395
113. Moorhead, G. B., Trinkle-Mulcahy, L., and Ulke-Lemee, A. (2007). Emerging roles of nuclear protein phosphatases. Nat. Rev. Mol. Cell Biol. 8, 234-244.
114. Morita, K., Saitoh, M., Tobiume, K., Matsuura, H., Enomoto, S., Nishitoh, H., et al. (2001). Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress. EMBO J. 20, 6028-6036.
115. Nakada, S., Chen, G. I., Gingras, A. C., and Durocher, D. (2008). PP4 is a gamma H2AX phosphatase required for recovery from the DNA damage checkpoint. EMBO Rep. 9, 1019-1026.
116. Nelson, D. A., Krucher, N. A., and Ludlow, J. W. (1997). High molecular weight protein phosphatase type 1 dephosphorylates the retinoblastoma protein. J. Biol. Chem. 272, 4528-4535.
117. Ng, C. P., Lee, H. C., Ho, C. W., Arooz, T., Siu, W. Y., Lau, A., et al. (2004). Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by their regulatory domains. J. Biol. Chem. 279, 8808-8819.
118. Niida, H., Katsuno, Y., Banerjee, B., Hande, M. P., and Nakanishi, M. (2007). Specific role of Chk1 phosphorylations in cell survival and checkpoint activation. Mol. Cell. Biol. 27, 2572-2581.
119. Oliva-Trastoy, M., Berthonaud, V., Chevalier, A., Ducrot, C., Marsolier-Kergoat, M. C., Mann, C., et al. (2007). The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase. Oncogene 26, 1449-1458.
120. Ollendorff, V., and Donoghue, D. J. (1997). The serine/threonine phosphatase PP5 interacts with CDC16 and CDC27, two tetratricopeptide repeat-containing subunits of the anaphase-promoting complex. J. Biol. Chem. 272, 32011-32018.
121. Olsen, J. V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., et al. (2006). Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635-648.
122. Paull, T. T., Rogakou, E. P., Yamazaki, V., Kirchgessner, C. U., Gellert, M., and Bonner, W. M. (2000). A critical role for histone H2AX in recruitment of repair factors to nuclear foci after DNA damage. Curr. Biol. 10, 886-895.
123. Pellegrini, M., Celeste, A., Difilippantonio, S., Guo, R., Wang, W., Feigenbaum, L., et al. (2006). Autophosphorylation at serine 1987 is dispensable for murine Atm activation in vivo. Nature 443, 222-225.
124. Peng, A., Lewellyn, A. L., Schiemann, W. P., and Maller, J. L. (2010). Repo-man controls a protein phosphatase 1-dependent threshold for DNA damage checkpoint activation. Curr. Biol. 20, 387-396.
125. Roos-Mattjus, P., Vroman, B. T., Burtelow, M. A., Rauen, M., Eapen, A. K., and Karnitz, L. M. (2002). Genotoxin-induced Rad9-Hus1-Rad1 (9-1-1) chromatin association is an early checkpoint signaling event. J. Biol. Chem. 277, 43809-43812.
126. Saito-Ohara, F., Imoto, I., Inoue, J., Hosoi, H., Nakagawara, A., Sugimoto, T., et al. (2003). PPM1D is a potential target for 17q gain in neuroblastoma. Cancer Res. 63, 1876-1883.
127. Sakasai, R., Shinohe, K., Ichijima, Y., Okita, N., Shibata, A., Asahina, K., et al. (2006). Differential involvement of phosphatidylinositol 3-kinase-related protein kinases in hyperphosphorylation of replication protein A2 in response to replication-mediated DNA double-strand breaks. Genes Cells 11, 237-246.
128. Sanchez, Y., Wong, C., Thoma, R. S., Richman, R., Wu, Z., Piwnica-Worms, H., et al. (1997). Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 277, 1497-1501.
129. Shieh, S. Y., Ahn, J., Tamai, K., Taya, Y., and Prives, C. (2000). The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev. 14, 289-300.
130. Shiloh, Y. (2003). ATM and related protein kinases: safeguarding genome integrity. Nat. Rev. Cancer 3, 155-168.
131. Shima, H., Haneji, T., Hatano, Y., Kasugai, I., Sugimura, T., and Nagao, M. (1993). Protein phosphatase 1 gamma 2 is associated with nuclei of meiotic cells in rat testis. Biochem. Biophys. Res. Commun. 194, 930-937.
132. Shimada, M., Haruta, M., Niida, H., Sawamoto, K., and Nakanishi, M. (2010). Protein phosphatase 1gamma is responsible for dephosphorylation of histone H3 at Thr 11 after DNA damage. EMBO Rep. 11, 883-889.
133. Shimada, M., and Nakanishi, M. (2008). Checkpoints meet the transcription at a novel histone milestone (H3-T11). Cell Cycle 7, 1555-1559.
134. Shimada, M., Niida, H., Zineldeen, D. H., Tagami, H., Tanaka, M., Saito, H., et al. (2008). Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression. Cell 132, 221-232.
135. Shreeram, S., Demidov, O. N., Hee, W. K., Yamaguchi, H., Onishi, N., Kek, C., et al. (2006). Wip1 phosphatase modulates ATM-dependent signaling pathways. Mol. Cell 23, 757-764.
136. Shroff, R., Arbel-Eden, A., Pilch, D., Ira, G., Bonner, W. M., Petrini, J. H., et al. (2004). Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break. Curr. Biol. 14, 1703-1711.
137. Shui, J. W., Hu, M. C., and Tan, T. H. (2007). Conditional knockout mice reveal an essential role of protein phosphatase 4 in thymocyte development and pre-T-cell receptor signaling. Mol. Cell. Biol. 27, 79-91.
138. Sumiyoshi, E., Sugimoto, A., and Yamamoto, M. (2002). Protein phosphatase 4 is required for centrosome maturation in mitosis and sperm meiosis in C. elegans. J. Cell Sci. 115, 1403-1410.
139. Silverstein, A. M., Galigniana, M. D., Chen, M. S., Owens-Grillo, J. K., Chinkers, M., and Pratt, W. B. (1997). Protein phosphatase 5 is a major component of glucocorticoid receptor.hsp90 complexes with properties of an FK506-binding immunophilin. J. Biol. Chem. 272, 16224-16230.
140. Smits, V. A., Reaper, P. M., and Jackson, S. P. (2006). Rapid PIKK-dependent release of Chk1 from chromatin promotes the DNA-damage checkpoint response. Curr. Biol. 16, 150-159.
141. Smolka, M. B., Albuquerque, C. P., Chen, S. H., and Zhou, H. (2007). Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases. Proc. Natl. Acad. Sci. U.S.A. 104, 10364-10369.
142. So, S., Davis, A. J., and Chen, D. J. (2009). Autophosphorylation at serine 1981 stabilizes ATM at DNA damage sites. J. Cell Biol. 187, 977-990.
143. Stefansson, B., and Brautigan, D. L. (2006). Protein phosphatase 6 subunit with conserved Sit4-associated protein domain targets IkappaBepsilon. J. Biol. Chem. 281, 22624-22634.
144. Stefansson, B., and Brautigan, D. L. (2007). Protein phosphatase PP6 N terminal domain restricts G1 to S phase progression in human cancer cells. Cell Cycle 6, 1386-1392.
145. Stefansson, B., Ohama, T., Daugherty, A. E., and Brautigan, D. L. (2008). Protein phosphatase 6 regulatory subunits composed of ankyrin repeat domains. Biochemistry 47, 1442-1451.
146. Stiff, T., O'Driscoll, M., Rief, N., Iwabuchi, K., Lobrich, M., and Jeggo, P. A. (2004). ATM and DNA-PK function redundantly to phosphorylate H2AX after exposure to ionizing radiation. Cancer Res. 64, 2390-2396.
147. Stokes, M. P., Rush, J., Macneill, J., Ren, J. M., Sprott, K., Nardone, J., et al. (2007). Profiling of UV-induced ATM/ATR signaling pathways. Proc. Natl. Acad. Sci. U.S.A. 104, 19855-19860.
148. Takekawa, M., Adachi, M., Nakahata, A., Nakayama, I., Itoh, F., Tsukuda, H., et al. (2000). p53-inducible wip1 phosphatase mediates a negative feedback regulation of p38 MAPK-p53 signaling in response to UV radiation. EMBO J. 19, 6517-6526.
149. Tang, X., Hui, Z. G., Cui, X. L., Garg, R., Kastan, M. B., and Xu, B. (2008). A novel ATM-dependent pathway regulates protein phosphatase 1 in response to DNA damage. Mol. Cell. Biol. 28, 2559-2566.
150. Tibbetts, R. S., Cortez, D., Brumbaugh, K. M., Scully, R., Livingston, D., Elledge, S. J., et al. (2000). Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Genes Dev. 14, 2989-3002.
151. Trinkle-Mulcahy, L., Andersen, J., Lam, Y. W., Moorhead, G., Mann, M., and Lamond, A. I. (2006). Repo-Man recruits PP1 gamma to chromatin and is essential for cell viability. J. Cell Biol. 172, 679-692.
152. Udho, E., Tedesco, V. C., Zygmunt, A., and Krucher, N. A. (2002). PNUTS (phosphatase nuclear targeting subunit) inhibits retinoblastoma-directed PP1 activity. Biochem. Biophys. Res. Commun. 297, 463-467.
153. Uziel, T., Lerenthal, Y., Moyal, L., Andegeko, Y., Mittelman, L., and Shiloh, Y. (2003). Requirement of the MRN complex for ATM activation by DNA damage. EMBO J. 22, 5612-5621.
154. Vagnarelli, P., Hudson, D. F., Ribeiro, S. A., Trinkle-Mulcahy, L., Spence, J. M., Lai, F., et al. (2006). Condensin and Repo-Man-PP1 co-operate in the regulation of chromosome architecture during mitosis. Nat. Cell Biol. 8, 1133-1142.
155. Varmuza, S., Jurisicova, A., Okano, K., Hudson, J., Boekelheide, K., and Shipp, E. B. (1999). Spermiogenesis is impaired in mice bearing a targeted mutation in the protein phosphatase 1cgamma gene. Dev. Biol. 205, 98-110.
156. Vietri, M., Bianchi, M., Ludlow, J. W., Mittnacht, S., and Villa-Moruzzi, E. (2006). Direct interaction between the catalytic subunit of Protein Phosphatase 1 and pRb. Cancer Cell Int. 6, 3.
157. Virshup, D. M., and Shenolikar, S. (2009). From promiscuity to precision: protein phosphatases get a makeover. Mol. Cell 33, 537-545.
158. Wang, H., Guan, J., Wang, H., Perrault, A. R., Wang, Y., and Iliakis, G. (2001). Replication protein A2 phosphorylation after DNA damage by the coordinated action of ataxia telangiectasia-mutated and DNA-dependent protein kinase. Cancer Res. 61, 8554-8563.
159. Wang, Q., Gao, F., Wang, T., Flagg, T., and Deng, X. (2009). A nonhomologous end-joining pathway is required for protein phosphatase 2A promotion of DNA double-strand break repair. Neoplasia 11, 1012-1021.
160. Wang, X., Zou, L., Lu, T., Bao, S., Hurov, K. E., Hittelman, W. N., et al. (2006). Rad17 phosphorylation is required for claspin recruitment and Chk1 activation in response to replication stress. Mol. Cell 23, 331-341.
161. Ward, I. M., and Chen, J. (2001). Histone H2AX is phosphorylated in an ATR-dependent manner in response to replicational stress. J. Biol. Chem. 276, 47759-47762.
162. Wechsler, T., Chen, B. P., Harper, R., Morotomi-Yano, K., Huang, B. C., Meek, K., et al. (2004). DNA-PKcs function regulated specifically by protein phosphatase 5. Proc. Natl. Acad. Sci. U.S.A. 101, 1247-1252.
163. Xu, X., Tsvetkov, L. M., and Stern, D. F. (2002). Chk2 activation and phosphorylation-dependent oligomerization. Mol. Cell. Biol. 22, 4419-4432.
164. Yamaguchi, H., Durell, S. R., Chatterjee, D. K., Anderson, C. W., and Appella, E. (2007). The Wip1 phosphatase PPM1D dephosphorylates SQ/TQ motifs in checkpoint substrates phosphorylated by PI3K-like kinases. Biochemistry 46, 12594-12603.
165. Yan, Y., Cao, P. T., Greer, P. M., Nagengast, E. S., Kolb, R. H., Mumby, M. C., et al. (2010). Protein phosphatase 2A has an essential role in the activation of gamma-irradiation-induced G2/M checkpoint response. Oncogene 29, 4317-4329.
166. Yong, W., Bao, S., Chen, H., Li, D., Sanchez, E. R., and Shou, W. (2007). Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia mutated (ATM)-mediated cell cycle arrest. J. Biol. Chem. 282, 14690-14694.
167. Zeng, K., Bastos, R. N., Barr, F. A., and Gruneberg, U. (2010). Protein phosphatase 6 regulates mitotic spindle formation by controlling the T-loop phosphorylation state of Aurora A bound to its activator TPX2. J. Cell Biol. 191, 1315-1332.
168. Zhang, J., Bao, S., Furumai, R., Kucera, K. S., Ali, A., Dean, N. M., et al. (2005). Protein phosphatase 5 is required for ATR-mediated checkpoint activation. Mol. Cell. Biol. 25, 9910-9919.
169. Zhao, H., and Piwnica-Worms, H. (2001). ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol. Cell. Biol. 21, 4129-4139.
170. Zhong, J., Liao, J., Liu, X., Wang, P., Liu, J., Hou, W., et al. (2011). Protein phosphatase PP6 is required for homology-directed repair of DNA double-strand breaks. Cell Cycle 10, 1411-1419.
171. Ziv, Y., Bielopolski, D., Galanty, Y., Lukas, C., Taya, Y., Schultz, D. C., et al. (2006). Chromatin relaxation in response to DNA double-strand breaks is modulated by a novel ATM- and KAP-1 dependent pathway. Nat. Cell Biol. 8, 870-876.
172. Zou, L., and Elledge, S. J. (2003). Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 300, 1542-1548.
173. Zuo, Z., Dean, N. M., and Honkanen, R. E. (1998). Serine/threonine protein phosphatase type 5 acts upstream of p53 to regulate the induction of p21(WAF1/Cip1) and mediate growth arrest. J. Biol. Chem. 273, 12250-12258.