Roles of Chk1 in cell biology and cancer therapy

International Journal of Cancer

Volumn 134, Issue 5, 2014, Pages 1013-1023

  Zhang, Youwei ^a   Hunter, Tony ^b  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b SALK INSTITUTE FOR BIOLOGICAL STUDIES   (United States)

Author keywords

cancer; cancer therapy; cell cycle checkpoints; Chk1

Indexed keywords

ANTINEOPLASTIC AGENT; CHECKPOINT KINASE 1; DNA; HISTONE DEACETYLASE INHIBITOR;

CANCER INHIBITION; CANCER THERAPY; CELL CYCLE ARREST; CELL CYCLE CHECKPOINT; CELL CYCLE M PHASE; CELL CYCLE S PHASE; CONFORMATIONAL TRANSITION; CYTOLOGY; DNA DAMAGE; DNA REPLICATION; DRUG TARGETING; ENZYME ACTIVATION; G2 PHASE CELL CYCLE CHECKPOINT; GENETIC CONSERVATION; HUMAN; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROCESSING; PROTEIN PROTEIN INTERACTION; PROTEIN SYNTHESIS INHIBITION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; TRANSCRIPTION REGULATION; TUMOR GROWTH;

CANCER; CANCER THERAPY; CELL CYCLE CHECKPOINTS; CHK1;

CELL CYCLE; DNA REPLICATION; DRUG RESISTANCE, NEOPLASM; ENZYME ACTIVATION; HUMANS; NEOPLASMS; PHOSPHORYLATION; PROTEIN CONFORMATION; PROTEIN KINASES;

EID: 84890555023     PISSN: 00207136     EISSN: 10970215     Source Type: Journal    
DOI: 10.1002/ijc.28226     Document Type: Review

References (197)

1. Ben-Yehoyada M, Wang LC, Kozekov ID, et al. Checkpoint signaling from a single DNA interstrand crosslink. Mol Cell 2009; 35: 704-15.
2. Cuadrado M, Martinez-Pastor B, Murga M, et al. ATM regulates ATR chromatin loading in response to DNA double-strand breaks. J Exp Med 2006; 203: 297-303.
3. Myers JS, Cortez D,. Rapid activation of ATR by ionizing radiation requires ATM and Mre11. J Biol Chem 2006; 281: 9346-50.
4. Jazayeri A, Falck J, Lukas C, et al. ATM- and cell cycle-dependent regulation of ATR in response to DNA double-strand breaks. Nat Cell Biol 2006; 8: 37-45.
5. Heffernan TP, Simpson DA, Frank AR, et al. An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage. Mol Cell Biol 2002; 22: 8552-61.
6. Cha RS, Kleckner N,. ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones. Science 2002; 297: 602-6.
7. Casper AM, Nghiem P, Arlt MF, et al. ATR regulates fragile site stability. Cell 2002; 111: 779-89.
8. Roshal M, Kim B, Zhu Y, et al. Activation of the ATR-mediated DNA damage response by the HIV-1 viral protein R. J Biol Chem 2003; 278: 25879-86.
9. Zimmerman ES, Sherman MP, Blackett JL, et al. Human immunodeficiency virus type 1 Vpr induces DNA replication stress in vitro and in vivo. J Virol 2006; 80: 10407-18.
10. Walworth N, Davey S, Beach D,. Fission yeast chk1 protein kinase links the rad checkpoint pathway to cdc2. Nature 1993; 363: 368-71.
11. al-Khodairy F, Fotou E, Sheldrick KS, et al. Identification and characterization of new elements involved in checkpoint and feedback controls in fission yeast. Mol Biol Cell 1994; 5: 147-60.
12. Fogarty P, Campbell SD, Abu-Shumays R, et al. The Drosophila grapes gene is related to checkpoint gene chk1/rad27 and is required for late syncytial division fidelity. Curr Biol 1997; 7: 418-26.
13. Sanchez Y, Wong C, Thoma RS, et al. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 1997; 277: 1497-501.
14. Peng CY, Graves PR, Thoma RS, et al. Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science 1997; 277: 1501-5.
15. Flaggs G, Plug AW, Dunks KM, et al. Atm-dependent interactions of a mammalian chk1 homolog with meiotic chromosomes. Curr Biol 1997; 7: 977-86.
16. Walworth NC, Bernards R,. rad-dependent response of the chk1-encoded protein kinase at the DNA damage checkpoint. Science 1996; 271: 353-6.
17. Kumagai A, Guo Z, Emami KH, et al. The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts. J Cell Biol 1998; 142: 1559-69.
18. Sarkaria JN, Busby EC, Tibbetts RS, et al. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res 1999; 59: 4375-82.
19. Moser BA, Brondello JM, Baber-Furnari B, et al. Mechanism of caffeine-induced checkpoint override in fission yeast. Mol Cell Biol 2000; 20: 4288-94.
20. Liu Q, Guntuku S, Cui XS, et al. Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint. Genes Dev 2000; 14: 1448-59.
21. Zhao H, Piwnica-Worms H,. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol Cell Biol 2001; 21: 4129-39.
22. Walker M, Black EJ, Oehler V, et al. Chk1 C-terminal regulatory phosphorylation mediates checkpoint activation by de-repression of Chk1 catalytic activity. Oncogene 2009; 28: 2314-23.
23. Guo Z, Kumagai A, Wang SX, et al. Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts. Genes Dev 2000; 14: 2745-56.
24. Lopez-Girona A, Tanaka K, Chen XB, et al. Serine-345 is required for Rad3-dependent phosphorylation and function of checkpoint kinase Chk1 in fission yeast. Proc Natl Acad Sci USA 2001; 98: 11289-94.
25. Cimprich KA, Cortez D,. ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 2008; 9: 616-27.
26. Xu X, Lee J, Stern DF,. Microcephalin is a DNA damage response protein involved in regulation of CHK1 and BRCA1. J Biol Chem 2004; 279: 34091-4.
27. Yarden RI, Pardo-Reoyo S, Sgagias M, et al. BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage. Nat Genet 2002; 30: 285-9.
28. Stauffer D, Chang B, Huang J, et al. p300/CREB-binding protein interacts with ATR and is required for the DNA replication checkpoint. J Biol Chem 2007; 282: 9678-87.
29. Yoo HY, Jeong SY, Dunphy WG,. Site-specific phosphorylation of a checkpoint mediator protein controls its responses to different DNA structures. Genes Dev 2006; 20: 772-83.
30. Sato K, Sundaramoorthy E, Rajendra E, et al. A DNA-damage selective role for BRCA1 E3 ligase in claspin ubiquitylation, CHK1 activation, and DNA repair. Curr Biol 2012; 22: 1659-66.
31. Capasso H, Palermo C, Wan S, et al. Phosphorylation activates Chk1 and is required for checkpoint-mediated cell cycle arrest. J Cell Sci 2002; 115: 4555-64.
32. Niida H, Katsuno Y, Banerjee B, et al. Specific role of Chk1 phosphorylations in cell survival and checkpoint activation. Mol Cell Biol 2007; 27: 2572-81.
33. Wilsker D, Petermann E, Helleday T, et al. Essential function of Chk1 can be uncoupled from DNA damage checkpoint and replication control. Proc Natl Acad Sci USA 2008; 105: 20752-7.
34. Wang J, Han X, Zhang Y,. Autoregulatory mechanisms of phosphorylation of checkpoint kinase 1. Cancer Res 2012; 72: 3786-94.
35. Kosoy A, O'Connell MJ,. Regulation of Chk1 by its C-terminal domain. Mol Biol Cell 2008; 19: 4546-53.
36. Falck J, Mailand N, Syljuasen RG, et al. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature 2001; 410: 842-7.
37. Sorensen CS, Syljuasen RG, Falck J, et al. Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer Cell 2003; 3: 247-58.
38. Shimuta K, Nakajo N, Uto K, et al. Chk1 is activated transiently and targets Cdc25A for degradation at the Xenopus midblastula transition. EMBO J 2002; 21: 3694-703.
39. Zhao H, Watkins JL, Piwnica-Worms H,. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci USA 2002; 99: 14795-800.
40. Mailand N, Falck J, Lukas C, et al. Rapid destruction of human Cdc25A in response to DNA damage. Science 2000; 288: 1425-9.
41. Liu P, Barkley LR, Day T, et al. The Chk1-mediated S-phase checkpoint targets initiation factor Cdc45 via a Cdc25A/Cdk2-independent mechanism. J Biol Chem 2006; 281: 30631-44.
42. Syljuasen RG, Sorensen CS, Hansen LT, et al. Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage. Mol Cell Biol 2005; 25: 3553-62.
43. Unsal-Kacmaz K, Mullen TE, Kaufmann WK, et al. Coupling of human circadian and cell cycles by the timeless protein. Mol Cell Biol 2005; 25: 3109-16.
44. Scorah J, Dong MQ, Yates JR, III, et al. A conserved proliferating cell nuclear antigen-interacting protein sequence in Chk1 is required for checkpoint function. J Biol Chem 2008; 283: 17250-9.
45. Taricani L, Shanahan F, Parry D,. Replication stress activates DNA polymerase alpha-associated Chk1. Cell Cycle 2009; 8: 482-9.
46. Lopes M, Cotta-Ramusino C, Pellicioli A, et al. The DNA replication checkpoint response stabilizes stalled replication forks. Nature 2001; 412: 557-61.
47. Feijoo C, Hall-Jackson C, Wu R, et al. Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing. J Cell Biol 2001; 154: 913-23.
48. Tercero JA, Diffley JF,. Regulation of DNA replication fork progression through damaged DNA by the Mec1/Rad53 checkpoint. Nature 2001; 412: 553-7.
49. Zachos G, Rainey MD, Gillespie DA,. Chk1-deficient tumour cells are viable but exhibit multiple checkpoint and survival defects. EMBO J 2003; 22: 713-23.
50. Petermann E, Maya-Mendoza A, Zachos G, et al. Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase. Mol Cell Biol 2006; 26: 3319-26.
51. Katsuno Y, Suzuki A, Sugimura K, et al. Cyclin A-Cdk1 regulates the origin firing program in mammalian cells. Proc Natl Acad Sci USA 2009; 106: 3184-9.
52. Petermann E, Woodcock M, Helleday T,. Chk1 promotes replication fork progression by controlling replication initiation. Proc Natl Acad Sci USA 2010; 107: 16090-5.
53. Conti C, Seiler JA, Pommier Y,. The mammalian DNA replication elongation checkpoint: implication of Chk1 and relationship with origin firing as determined by single DNA molecule and single cell analyses. Cell Cycle 2007; 6: 2760-7.
54. Liu S, Bekker-Jensen S, Mailand N, et al. Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation. Mol Cell Biol 2006; 26: 6056-64.
55. Forment JV, Blasius M, Guerini I, et al. Structure-specific DNA endonuclease Mus81/Eme1 generates DNA damage caused by Chk1 inactivation. PLoS One 2011; 6: e23517.
56. Zhang YW, Otterness DM, Chiang GG, et al. Genotoxic stress targets human Chk1 for degradation by the ubiquitin-proteasome pathway. Mol Cell 2005; 19: 607-18.
57. O'Connell MJ, Raleigh JM, Verkade HM, et al. Chk1 is a wee1 kinase in the G2 DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation. EMBO J 1997; 16: 545-54.
58. Rhind N, Furnari B, Russell P,. Cdc2 tyrosine phosphorylation is required for the DNA damage checkpoint in fission yeast. Genes Dev 1997; 11: 504-11.
59. Furnari B, Rhind N, Russell P,. Cdc25 mitotic inducer targeted by chk1 DNA damage checkpoint kinase. Science 1997; 277: 1495-7.
60. Lopez-Girona A, Furnari B, Mondesert O, et al. Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein. Nature 1999; 397: 172-5.
61. Lopez-Girona A, Kanoh J, Russell P,. Nuclear exclusion of Cdc25 is not required for the DNA damage checkpoint in fission yeast. Curr Biol 2001; 11: 50-4.
62. Mailand N, Bekker-Jensen S, Bartek J, et al. Destruction of Claspin by SCFbetaTrCP restrains Chk1 activation and facilitates recovery from genotoxic stress. Mol Cell 2006; 23: 307-18.
63. Peschiaroli A, Dorrello NV, Guardavaccaro D, et al. SCFbetaTrCP-mediated degradation of Claspin regulates recovery from the DNA replication checkpoint response. Mol Cell 2006; 23: 319-29.
64. Xu N, Hegarat N, Black EJ, et al. Akt/PKB suppresses DNA damage processing and checkpoint activation in late G2. J Cell Biol 2010; 190: 297-305.
65. Shiromizu T, Goto H, Tomono Y, et al. Regulation of mitotic function of Chk1 through phosphorylation at novel sites by cyclin-dependent kinase 1 (Cdk1). Genes Cells 2006; 11: 477-85.
66. Peddibhotla S, Lam MH, Gonzalez-Rimbau M, et al. The DNA-damage effector checkpoint kinase 1 is essential for chromosome segregation and cytokinesis. Proc Natl Acad Sci USA 2009; 106: 5159-64.
67. Enomoto M, Goto H, Tomono Y, et al. Novel positive feedback loop between Cdk1 and Chk1 in the nucleus during G2/M transition. J Biol Chem 2009; 284: 34223-30.
68. Tang J, Erikson RL, Liu X,. Checkpoint kinase 1 (Chk1) is required for mitotic progression through negative regulation of polo-like kinase 1 (Plk1). Proc Natl Acad Sci USA 2006; 103: 11964-9.
69. Zachos G, Black EJ, Walker M, et al. Chk1 is required for spindle checkpoint function. Dev Cell 2007; 12: 247-60.
70. Krystyniak A, Garcia-Echeverria C, Prigent C, et al. Inhibition of Aurora A in response to DNA damage. Oncogene 2006; 25: 338-48.
71. Yu KR, Saint RB, Sullivan W,. The Grapes checkpoint coordinates nuclear envelope breakdown and chromosome condensation. Nat Cell Biol 2000; 2: 609-15.
72. Royou A, Macias H, Sullivan W,. The Drosophila Grp/Chk1 DNA damage checkpoint controls entry into anaphase. Curr Biol 2005; 15: 334-9.
73. Kramer A, Mailand N, Lukas C, et al. Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase. Nat Cell Biol 2004; 6: 884-91.
74. Matsuyama M, Goto H, Kasahara K, et al. Nuclear Chk1 prevents premature mitotic entry. J Cell Sci 2011; 124: 2113-19.
75. Shimada M, Niida H, Zineldeen DH, et al. Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression. Cell 2008; 132: 221-32.
76. Takai H, Tominaga K, Motoyama N, et al. Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice. Genes Dev 2000; 14: 1439-47.
77. Sorensen CS, Hansen LT, Dziegielewski J, et al. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol 2005; 7: 195-201.
78. Shtivelman E, Sussman J, Stokoe D,. A role for PI 3-kinase and PKB activity in the G2/M phase of the cell cycle. Curr Biol 2002; 12: 919-24.
79. Li P, Goto H, Kasahara K, et al. P90 RSK arranges Chk1 in the nucleus for monitoring of genomic integrity during cell proliferation. Mol Biol Cell 2012; 23: 1582-92.
80. Hammond EM, Denko NC, Dorie MJ, et al. Hypoxia links ATR and p53 through replication arrest. Mol Cell Biol 2002; 22: 1834-43.
81. Das KC, Dashnamoorthy R,. Hyperoxia activates the ATR-Chk1 pathway and phosphorylates p53 at multiple sites. Am J Physiol Lung Cell Mol Physiol 2004; 286: L87-L97.
82. Furusawa Y, Iizumi T, Fujiwara Y, et al. Inhibition of checkpoint kinase 1 abrogates G2/M checkpoint activation and promotes apoptosis under heat stress. Apoptosis 2012; 17: 102-12.
83. Malzer E, Daly ML, Moloney A, et al. Impaired tissue growth is mediated by checkpoint kinase 1 (CHK1) in the integrated stress response. J Cell Sci 2010; 123: 2892-900.
84. Katsuragi Y, Sagata N,. Regulation of Chk1 kinase by autoinhibition and ATR-mediated phosphorylation. Mol Biol Cell 2004; 15: 1680-9.
85. Zhang YW, Brognard J, Coughlin C, et al. The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress. Mol Cell 2009; 35: 442-53.
86. Palermo C, Hope JC, Freyer GA, et al. Importance of a C-terminal conserved region of Chk1 for checkpoint function. PLoS One 2008; 3: e1427.
87. Smits VA, Reaper PM, Jackson SP,. Rapid PIKK-dependent release of Chk1 from chromatin promotes the DNA-damage checkpoint response. Curr Biol 2006; 16: 150-9.
88. Chen P, Luo C, Deng Y, et al. The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation. Cell 2000; 100: 681-92.
89. Boggon TJ, Eck MJ,. Structure and regulation of Src family kinases. Oncogene 2004; 23: 7918-27.
90. Gallagher PJ, Herring BP, Trafny A, et al. A molecular mechanism for autoinhibition of myosin light chain kinases. J Biol Chem 1993; 268: 26578-82.
91. Bekker-Jensen S, Lukas C, Kitagawa R, et al. Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks. J Cell Biol 2006; 173: 195-206.
92. Huh J, Piwnica-Worms H,. CRL4CDT2 targets CHK1 for PCNA-independent destruction. Mol Cell Biol 2013; 33: 213-26.
93. Leung-Pineda V, Huh J, Piwnica-Worms H,. DDB1 targets Chk1 to the Cul4 E3 ligase complex in normal cycling cells and in cells experiencing replication stress. Cancer Res 2009; 69: 2630-7.
94. Chen L, Liu TH, Walworth NC,. Association of Chk1 with 14-3-3 proteins is stimulated by DNA damage. Genes Dev 1999; 13: 675-85.
95. Jiang K, Pereira E, Maxfield M, et al. Regulation of Chk1 includes chromatin association and 14-3-3 binding following phosphorylation on Ser-345. J Biol Chem 2003; 278: 25207-17.
96. Dunaway S, Liu HY, Walworth NC,. Interaction of 14-3-3 protein with Chk1 affects localization and checkpoint function. J Cell Sci 2005; 118: 39-50.
97. Merry C, Fu K, Wang J, et al. Targeting the checkpoint kinase Chk1 in cancer therapy. Cell Cycle 2010; 9: 279-83.
98. Stracker TH, Usui T, Petrini JH,. Taking the time to make important decisions: the checkpoint effector kinases Chk1 and Chk2 and the DNA damage response. DNA Repair (Amst) 2009; 8: 1047-54.
99. Wang J, Han X, Feng X, et al. Coupling cellular localization and function of checkpoint kinase 1 (chk1) in checkpoints and cell viability. J Biol Chem 2012; 287: 25501-9.
100. Haruki N, Saito H, Tatematsu Y, et al. Histological type-selective, tumor-predominant expression of a novel CHK1 isoform and infrequent in vivo somatic CHK2 mutation in small cell lung cancer. Cancer Res 2000; 60: 4689-92.
101. Shann YJ, Hsu MT,. Cloning and characterization of liver-specific isoform of Chk1 gene from rat. J Biol Chem 2001; 276: 48863-70.
102. Pabla N, Bhatt K, Dong Z,. Checkpoint kinase 1 (Chk1)-short is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints. Proc Natl Acad Sci USA 2012; 109: 197-202.
103. Okita N, Kudo Y, Tanuma S,. Checkpoint kinase 1 is cleaved in a caspase-dependent pathway during genotoxic stress-induced apoptosis. Biol Pharm Bull 2007; 30: 359-62.
104. Matsuura K, Wakasugi M, Yamashita K, et al. Cleavage-mediated activation of Chk1 during apoptosis. J Biol Chem 2008; 283: 25485-91.
105. Kaneko YS, Watanabe N, Morisaki H, et al. Cell-cycle-dependent and ATM-independent expression of human Chk1 kinase. Oncogene 1999; 18: 3673-81.
106. Carrassa L, Broggini M, Vikhanskaya F, et al. Characterization of the 5'flanking region of the human Chk1 gene: identification of E2F1 functional sites. Cell Cycle 2003; 2: 604-9.
107. Gottifredi V, Karni-Schmidt O, Shieh SS, et al. p53 down-regulates CHK1 through p21 and the retinoblastoma protein. Mol Cell Biol 2001; 21: 1066-76.
108. Guervilly JH, Renaud E, Takata M, et al. USP1 deubiquitinase maintains phosphorylated CHK1 by limiting its DDB1-dependent degradation. Hum Mol Genet 2011; 20: 2171-81.
109. Brazelle W, Kreahling JM, Gemmer J, et al. Histone deacetylase inhibitors downregulate checkpoint kinase 1 expression to induce cell death in non-small cell lung cancer cells. PLoS One 2010; 5: e14335.
110. Kim AJ, Kim HJ, Jee HJ, et al. Glucose deprivation is associated with Chk1 degradation through the ubiquitin-proteasome pathway and effective checkpoint response to replication blocks. Biochim Biophys Acta 2011; 1813: 1230-8.
111. Arlander SJ, Eapen AK, Vroman BT, et al. Hsp90 inhibition depletes Chk1 and sensitizes tumor cells to replication stress. J Biol Chem 2003; 278: 52572-7.
112. Kim KS, Choi KJ, Bae S,. Interferon-gamma enhances radiation-induced cell death via downregulation of Chk1. Cancer Biol Ther 2012; 13: 1018-25.
113. Luke-Glaser S, Luke B, Grossi S, et al. FANCM regulates DNA chain elongation and is stabilized by S-phase checkpoint signalling. EMBO J 2010; 29: 795-805.
114. Lin SY, Rai R, Li K, et al. BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1-Chk1 pathway, implicating checkpoint dysfunction in microcephaly. Proc Natl Acad Sci USA 2005; 102: 15105-9.
115. Collis SJ, Barber LJ, Clark AJ, et al. HCLK2 is essential for the mammalian S-phase checkpoint and impacts on Chk1 stability. Nat Cell Biol 2007; 9: 391-401.
116. Li DQ, Ohshiro K, Khan MN, et al. Requirement of MTA1 in ATR-mediated DNA damage checkpoint function. J Biol Chem 2010; 285: 19802-12.
117. Lam MH, Liu Q, Elledge SJ, et al. Chk1 is haploinsufficient for multiple functions critical to tumor suppression. Cancer Cell 2004; 6: 45-59.
118. Zaugg K, Su YW, Reilly PT, et al. Cross-talk between Chk1 and Chk2 in double-mutant thymocytes. Proc Natl Acad Sci USA 2007; 104: 3805-10.
119. Greenow KR, Clarke AR, Jones RH,. Chk1 deficiency in the mouse small intestine results in p53-independent crypt death and subsequent intestinal compensation. Oncogene 2009; 28: 1443-53.
120. Boles NC, Peddibhotla S, Chen AJ, et al. Chk1 haploinsufficiency results in anemia and defective erythropoiesis. PLoS One 2010; 5: e8581.
121. O'Neill T, Giarratani L, Chen P, et al. Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the oriented peptide library approach. J Biol Chem 2002; 277: 16102-15.
122. Kim MA, Kim HJ, Brown AL, et al. Identification of novel substrates for human checkpoint kinase Chk1 and Chk2 through genome-wide screening using a consensus Chk phosphorylation motif. Exp Mol Med 2007; 39: 205-12.
123. Blasius M, Forment JV, Thakkar N, et al. A phospho-proteomic screen identifies substrates of the checkpoint kinase Chk1. Genome Biol 2011; 12: R78.
124. Chen MS, Ryan CE, Piwnica-Worms H,. Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding. Mol Cell Biol 2003; 23: 7488-97.
125. Uto K, Inoue D, Shimuta K, et al. Chk1, but not Chk2, inhibits Cdc25 phosphatases by a novel common mechanism. EMBO J 2004; 23: 3386-96.
126. Schmitt E, Boutros R, Froment C, et al. CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage. J Cell Sci 2006; 119: 4269-75.
127. Shieh SY, Ahn J, Tamai K, et al. The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev 2000; 14: 289-300.
128. Craig AL, Chrystal JA, Fraser JA, et al. The MDM2 ubiquitination signal in the DNA-binding domain of p53 forms a docking site for calcium calmodulin kinase superfamily members. Mol Cell Biol 2007; 27: 3542-55.
129. Jin Y, Dai MS, Lu SZ, et al. 14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1, resulting in p53 activation. EMBO J 2006; 25: 1207-18.
130. Melixetian M, Klein DK, Sorensen CS, et al. NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint. Nat Cell Biol 2009; 11: 1247-53.
131. Sanchez Y, Bachant J, Wang H, et al. Control of the DNA damage checkpoint by chk1 and rad53 protein kinases through distinct mechanisms. Science 1999; 286: 1166-71.
132. Wang H, Liu D, Wang Y, et al. Pds1 phosphorylation in response to DNA damage is essential for its DNA damage checkpoint function. Genes Dev 2001; 15: 1361-72.
133. Lee J, Kumagai A, Dunphy WG,. Positive regulation of Wee1 by Chk1 and 14-3-3 proteins. Mol Biol Cell 2001; 12: 551-63.
134. Groth A, Lukas J, Nigg EA, et al. Human Tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint. EMBO J 2003; 22: 1676-87.
135. Hu C, Zhang S, Gao X, et al. Roles of Kruppel-associated Box (KRAB)-associated co-repressor KAP1 Ser-473 phosphorylation in DNA damage response. J Biol Chem 2012; 287: 18937-52.
136. Clarke CA, Clarke PR,. DNA-dependent phosphorylation of Chk1 and Claspin in a human cell-free system. Biochem J 2005; 388: 705-12.
137. Kasahara K, Goto H, Enomoto M, et al. 14-3-3gamma mediates Cdc25A proteolysis to block premature mitotic entry after DNA damage. EMBO J 2010; 29: 2802-12.
138. Petsalaki E, Akoumianaki T, Black EJ, et al. Phosphorylation at serine 331 is required for Aurora B activation. J Cell Biol 2011; 195: 449-66.
139. Sengupta S, Robles AI, Linke SP, et al. Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest. J Cell Biol 2004; 166: 801-13.
140. Kaur S, Modi P, Srivastava V, et al. Chk1-dependent constitutive phosphorylation of BLM helicase at serine 646 decreases after DNA damage. Mol Cancer Res 2010; 8: 1234-47.
141. Wang X, Kennedy RD, Ray K, et al. Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway. Mol Cell Biol 2007; 27: 3098-108.
142. Zhi G, Wilson JB, Chen X, et al. Fanconi anemia complementation group FANCD2 protein serine 331 phosphorylation is important for fanconi anemia pathway function and BRCA2 interaction. Cancer Res 2009; 69: 8775-83.
143. Hromas R, Williamson EA, Fnu S, et al. Chk1 phosphorylation of Metnase enhances DNA repair but inhibits replication fork restart. Oncogene 2012; 31: 4245-54.
144. Gonzalez S, Prives C, Cordon-Cardo C,. p73alpha regulation by Chk1 in response to DNA damage. Mol Cell Biol 2003; 23: 8161-71.
145. Ou YH, Chung PH, Sun TP, et al. p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the regulation of DNA-damage-induced C-terminal acetylation. Mol Biol Cell 2005; 16: 1684-95.
146. Rocha S, Garrett MD, Campbell KJ, et al. Regulation of NF-kappaB and p53 through activation of ATR and Chk1 by the ARF tumour suppressor. EMBO J 2005; 24: 1157-69.
147. Schmitt AM, Crawley CD, Kang S, et al. p50 (NF-kappaB1) is an effector protein in the cytotoxic response to DNA methylation damage. Mol Cell 2011; 44: 785-96.
148. Garate M, Campos EI, Bush JA, et al. Phosphorylation of the tumor suppressor p33(ING1b) at Ser-126 influences its protein stability and proliferation of melanoma cells. FASEB J 2007; 21: 3705-16.
149. Ullah Z, de Renty C, DePamphilis ML,. Checkpoint kinase 1 prevents cell cycle exit linked to terminal cell differentiation. Mol Cell Biol 2011; 31: 4129-43.
150. Kumagai A, Dunphy WG,. Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts. Mol Cell 2000; 6: 839-49.
151. Meng Z, Capalbo L, Glover DM, et al. Role for casein kinase 1 in the phosphorylation of Claspin on critical residues necessary for the activation of Chk1. Mol Biol Cell 2011; 22: 2834-47.
152. Galvan V, Kurakin AV, Bredesen DE,. Interaction of checkpoint kinase 1 and the X-linked inhibitor of apoptosis during mitosis. FEBS Lett 2004; 558: 57-62.
153. Han EK, Butler C, Zhang H, et al. Chkl binds and phosphorylates BAD protein. Anticancer Res 2004; 24: 3907-10.
154. Lu X, Nannenga B, Donehower LA,. PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints. Genes Dev 2005; 19: 1162-74.
155. Alderton GK, Galbiati L, Griffith E, et al. Regulation of mitotic entry by microcephalin and its overlap with ATR signalling. Nat Cell Biol 2006; 8: 725-33.
156. Palii SS, Van Emburgh BO, Sankpal UT, et al. DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B. Mol Cell Biol 2008; 28: 752-71.
157. Chen S, Maya-Mendoza A, Zeng K, et al. Interaction with checkpoint kinase 1 modulates the recruitment of nucleophosmin to chromatin. J Proteome Res 2009; 8: 4693-704.
158. Liu Y, Fang Y, Shao H, et al. Interactions of human mismatch repair proteins MutSalpha and MutLalpha with proteins of the ATR-Chk1 pathway. J Biol Chem 2010; 285: 5974-82.
159. Kosoy A, Calonge TM, Outwin EA, et al. Fission yeast Rnf4 homologs are required for DNA repair. J Biol Chem 2007; 282: 20388-94.
160. Sun TP, Shieh SY,. Human FEM1B is required for Rad9 recruitment and CHK1 activation in response to replication stress. Oncogene 2009; 28: 1971-81.
161. Bartek J, Lukas C, Lukas J,. Checking on DNA damage in S phase. Nat Rev Mol Cell Biol 2004; 5: 792-804.
162. Solyom S, Pylkas K, Winqvist R,. Screening for large genomic rearrangements of the BRIP1 and CHK1 genes in Finnish breast cancer families. Fam Cancer 2010; 9: 537-40.
163. Tort F, Hernandez S, Bea S, et al. Checkpoint kinase 1 (CHK1) protein and mRNA expression is downregulated in aggressive variants of human lymphoid neoplasms. Leukemia 2005; 19: 112-17.
164. Bertoni F, Codegoni AM, Furlan D, et al. CHK1 frameshift mutations in genetically unstable colorectal and endometrial cancers. Genes Chromosomes Cancer 1999; 26: 176-80.
165. Menoyo A, Alazzouzi H, Espin E, et al. Somatic mutations in the DNA damage-response genes ATR and CHK1 in sporadic stomach tumors with microsatellite instability. Cancer Res 2001; 61: 7727-30.
166. Kim CJ, Lee JH, Song JW, et al. Chk1 frameshift mutation in sporadic and hereditary non-polyposis colorectal cancers with microsatellite instability. Eur J Surg Oncol 2007; 33: 580-5.
167. Fishler T, Li YY, Wang RH, et al. Genetic instability and mammary tumor formation in mice carrying mammary-specific disruption of Chk1 and p53. Oncogene 2010; 29: 4007-17.
168. Tho LM, Libertini S, Rampling R, et al. Chk1 is essential for chemical carcinogen-induced mouse skin tumorigenesis. Oncogene 2012; 31: 1366-75.
169. Kawasumi M, Lemos B, Bradner JE, et al. Protection from UV-induced skin carcinogenesis by genetic inhibition of the ataxia telangiectasia and Rad3-related (ATR) kinase. Proc Natl Acad Sci USA 2011; 108: 13716-21.
170. Hong J, Hu K, Yuan Y, et al. CHK1 targets spleen tyrosine kinase (L) for proteolysis in hepatocellular carcinoma. J Clin Invest 2012; 122: 2165-75.
171. Cho SH, Toouli CD, Fujii GH, et al. Chk1 is essential for tumor cell viability following activation of the replication checkpoint. Cell Cycle 2005; 4: 131-9.
172. Madoz-Gurpide J, Canamero M, Sanchez L, et al. A proteomics analysis of cell signaling alterations in colorectal cancer. Mol Cell Proteomics 2007; 6: 2150-64.
173. Verlinden L, Vanden Bempt I, Eelen G, et al. The E2F-regulated gene Chk1 is highly expressed in triple-negative estrogen receptor /progesterone receptor /HER-2 breast carcinomas. Cancer Res 2007; 67: 6574-81.
174. Yao H, Yang Z, Li Y,. Expression of checkpoint kinase 1 and polo-like kinase 1 and its clinicopathological significance in benign and malignant lesions of the stomach. Zhong Nan Da Xue Xue Bao Yi Xue Ban 2010; 35: 1080-4.
175. Xu J, Li Y, Wang F, et al. Suppressed miR-424 expression via upregulation of target gene Chk1 contributes to the progression of cervical cancer. Oncogene 2013; 32: 976-87.
176. Sriuranpong V, Mutirangura A, Gillespie JW, et al. Global gene expression profile of nasopharyngeal carcinoma by laser capture microdissection and complementary DNA microarrays. Clin Cancer Res 2004; 10: 4944-58.
177. Lundgren K, Holm K, Nordenskjold B, et al. Gene products of chromosome 11q and their association with CCND1 gene amplification and tamoxifen resistance in premenopausal breast cancer. Breast Cancer Res 2008; 10: R81.
178. Lopez-Contreras AJ, Gutierrez-Martinez P, Specks J, et al. An extra allele of Chk1 limits oncogene-induced replicative stress and promotes transformation. J Exp Med 2012; 209: 455-61.
179. Perego P, Gatti L, Righetti SC, et al. Development of resistance to a trinuclear platinum complex in ovarian carcinoma cells. Int J Cancer 2003; 105: 617-24.
180. Bao S, Wu Q, McLendon RE, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 2006; 444: 756-60.
181. Cavelier C, Didier C, Prade N, et al. Constitutive activation of the DNA damage signaling pathway in acute myeloid leukemia with complex karyotype: potential importance for checkpoint targeting therapy. Cancer Res 2009; 69: 8652-61.
182. Lee JH, Choy ML, Ngo L, et al. Role of checkpoint kinase 1 (Chk1) in the mechanisms of resistance to histone deacetylase inhibitors. Proc Natl Acad Sci USA 2011; 108: 19629-34.
183. Bartucci M, Svensson S, Romania P, et al. Therapeutic targeting of Chk1 in NSCLC stem cells during chemotherapy. Cell Death Differ 2012; 19: 768-78.
184. Wang X, Ma Z, Xiao Z, et al. Chk1 knockdown confers radiosensitization in prostate cancer stem cells. Oncol Rep 2012; 28: 2247-54.
185. Seol HJ, Yoo HY, Jin J, et al. The expression of DNA damage checkpoint proteins and prognostic implication in metastatic brain tumors. Oncol Res 2011; 19: 381-90.
186. Roe OD, Szulkin A, Anderssen E, et al. Molecular resistance fingerprint of pemetrexed and platinum in a long-term survivor of mesothelioma. PLoS One 2012; 7: e40521.
187. Arora S, Bisanz KM, Peralta LA, et al. RNAi screening of the kinome identifies modulators of cisplatin response in ovarian cancer cells. Gynecol Oncol 2010; 118: 220-7.
188. Cole KA, Huggins J, Laquaglia M, et al. RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHK1) as a therapeutic target in neuroblastoma. Proc Natl Acad Sci USA 2011; 108: 3336-41.
189. Bennett CN, Tomlinson CC, Michalowski AM, et al. Cross-species genomic and functional analyses identify a combination therapy using a CHK1 inhibitor and a ribonucleotide reductase inhibitor to treat triple-negative breast cancer. Breast Cancer Res 2012; 14: R109.
190. Koniaras K, Cuddihy AR, Christopoulos H, et al. Inhibition of Chk1-dependent G2 DNA damage checkpoint radiosensitizes p53 mutant human cells. Oncogene 2001; 20: 7453-63.
191. Ma CX, Cai S, Li S, et al. Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models. J Clin Invest 2012; 122: 1541-52.
192. Dai Y, Grant S,. New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clin Cancer Res 2010; 16: 376-83.
193. Ma CX, Janetka JW, Piwnica-Worms H,. Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends Mol Med 2010; 17: 88-96.
194. Carrassa L, Damia G,. Unleashing Chk1 in cancer therapy. Cell Cycle 2011; 10: 2121-8.
195. Maugeri-Sacca M, Bartucci M, De Maria R,. Checkpoint kinase 1 inhibitors for potentiating systemic anticancer therapy. Cancer Treat Rev 2012; 39: 525-33.
196. Kristensen LP, Larsen MR, Hojrup P, et al. Phosphorylation of the regulatory beta-subunit of protein kinase CK2 by checkpoint kinase Chk1: identification of the in vitro CK2beta phosphorylation site. FEBS Lett 2004; 569: 217-23.
197. Liu HY, Nefsky BS, Walworth NC,. The Ded1 DEAD box helicase interacts with Chk1 and Cdc2. J Biol Chem 2002; 277: 2637-43.