Chk1

Summary

Gene Symbol: Chk1
Description: checkpoint kinase 1
Alias: CHK1, serine/threonine-protein kinase Chk1, CHK1 checkpoint homolog, Checkpoint, S. pombe, homolog of, 1, Chk1-S, cell cycle checkpoint kinase
Species: human

Top Publications

  1. ncbi The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons
    Karen Flatten
    Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    J Biol Chem 280:14349-55. 2005
  2. pmc Ubiquitin-specific peptidase 20 regulates Rad17 stability, checkpoint kinase 1 phosphorylation and DNA repair by homologous recombination
    Ilanchezhian Shanmugam
    From the Division of Hematology Oncology, Dept of Internal Medicine, and the Cancer Center, University of New Mexico, Albuquerque, New Mexico 87131
    J Biol Chem 289:22739-48. 2014
  3. pmc DDB1 targets Chk1 to the Cul4 E3 ligase complex in normal cycling cells and in cells experiencing replication stress
    Van Leung-Pineda
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri, USA
    Cancer Res 69:2630-7. 2009
  4. pmc Role of checkpoint kinase 1 (Chk1) in the mechanisms of resistance to histone deacetylase inhibitors
    Ju Hee Lee
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 108:19629-34. 2011
  5. pmc 4-Hydroxynonenal induces G2/M phase cell cycle arrest by activation of the ataxia telangiectasia mutated and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) signaling pathway
    Pankaj Chaudhary
    Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA
    J Biol Chem 288:20532-46. 2013
  6. ncbi Mitotic DNA damage response: Polo-like kinase-1 is dephosphorylated through ATM-Chk1 pathway
    Hee Jae Lee
    Laboratory of Cell Cycle and Signal Transduction, World Class University Research Department of Nanobiomedical Science, and Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, Korea
    Cell Cycle 9:2389-98. 2010
  7. doi PF-00477736 mediates checkpoint kinase 1 signaling pathway and potentiates docetaxel-induced efficacy in xenografts
    Cathy Zhang
    Oncology Research Unit, Pfizer Global Research and Development, La Jolla Laboratories, San Diego, California, USA
    Clin Cancer Res 15:4630-40. 2009
  8. ncbi Regulation of Chk1 includes chromatin association and 14-3-3 binding following phosphorylation on Ser-345
    Kecheng Jiang
    Department of Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, Ohio 45267 0524, USA
    J Biol Chem 278:25207-17. 2003
  9. pmc TAp73 induction by nitric oxide: regulation by checkpoint kinase 1 (CHK1) and protection against apoptosis
    Ali Tebbi
    Universite Paris Sud, Institute of Molecular and Cellular Biochemistry and Biophysics, UMR 8619, F 91405 Orsay, France
    J Biol Chem 286:7873-84. 2011
  10. doi HY-1 induces G(2)/M cell cycle arrest in human colon cancer cells through the ATR-Chk1-Cdc25C and Weel pathways
    Yu Zhao
    Institute of Nautical Medicine, Nantong University, Nantong, China
    Cancer Sci 104:1062-6. 2013

Research Grants

  1. Jac A Nickoloff; Fiscal Year: 2016
  2. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
  3. Peter M Burgers; Fiscal Year: 2015
  4. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
  5. You Wei Zhang; Fiscal Year: 2016
  6. Michael B Yaffe; Fiscal Year: 2016
  7. TONY R HUNTER; Fiscal Year: 2016
  8. Peter M Burgers; Fiscal Year: 2016
  9. CELL CYCLE CHECKPOINT CONTROL IN RESPONSE TO DNA DAMAGE
    Nancy C Walworth; Fiscal Year: 2011
  10. DISSECTION OF THE DNA DAMAGE CHECKPOINT PATHWAYS
    Yolanda Sanchez; Fiscal Year: 2009

Detail Information

Publications230 found, 100 shown here

  1. ncbi The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons
    Karen Flatten
    Division of Oncology Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    J Biol Chem 280:14349-55. 2005
    ..that both the ataxia telangiectasia mutated (ATM)/checkpoint kinase (Chk) 2 and ATM- and Rad 3-related (ATR)/Chk1 checkpoint pathways are activated after treatment with these agents...
  2. pmc Ubiquitin-specific peptidase 20 regulates Rad17 stability, checkpoint kinase 1 phosphorylation and DNA repair by homologous recombination
    Ilanchezhian Shanmugam
    From the Division of Hematology Oncology, Dept of Internal Medicine, and the Cancer Center, University of New Mexico, Albuquerque, New Mexico 87131
    J Biol Chem 289:22739-48. 2014
    Rad17 is a subunit of the Rad9-Hus1-Rad1 clamp loader complex, which is required for Chk1 activation after DNA damage. Rad17 has been shown to be regulated by the ubiquitin-proteasome system...
  3. pmc DDB1 targets Chk1 to the Cul4 E3 ligase complex in normal cycling cells and in cells experiencing replication stress
    Van Leung-Pineda
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri, USA
    Cancer Res 69:2630-7. 2009
    The Chk1 protein kinase preserves genome integrity in normal proliferating cells and in cells experiencing replicative and genotoxic stress. Chk1 is currently being targeted in anticancer regimens...
  4. pmc Role of checkpoint kinase 1 (Chk1) in the mechanisms of resistance to histone deacetylase inhibitors
    Ju Hee Lee
    Cell Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 108:19629-34. 2011
    ..In this study, we found that checkpoint kinase 1 (Chk1), a component of the G2 DNA damage checkpoint, is important in the resistance of normal cells to HDACi in vitro and ..
  5. pmc 4-Hydroxynonenal induces G2/M phase cell cycle arrest by activation of the ataxia telangiectasia mutated and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) signaling pathway
    Pankaj Chaudhary
    Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center, Fort Worth, Texas 76107, USA
    J Biol Chem 288:20532-46. 2013
    ..Cdc25C was regulated by activation of the ataxia telangiectasia and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1) pathway...
  6. ncbi Mitotic DNA damage response: Polo-like kinase-1 is dephosphorylated through ATM-Chk1 pathway
    Hee Jae Lee
    Laboratory of Cell Cycle and Signal Transduction, World Class University Research Department of Nanobiomedical Science, and Institute of Tissue Regeneration Engineering, Dankook University, Cheonan, Korea
    Cell Cycle 9:2389-98. 2010
    ..Inhibition of Plk1 through dephosphorylation was dependent on ATM/Chk1 activity. Depleted expression of ATM and Chk1 was achieved using small hairpin RNA (shRNA) plasmid constructs...
  7. doi PF-00477736 mediates checkpoint kinase 1 signaling pathway and potentiates docetaxel-induced efficacy in xenografts
    Cathy Zhang
    Oncology Research Unit, Pfizer Global Research and Development, La Jolla Laboratories, San Diego, California, USA
    Clin Cancer Res 15:4630-40. 2009
    Checkpoint kinase 1 (Chk1) plays a critical role in the activation of mitotic spindle checkpoint and DNA damage checkpoint. We examined the preclinical use of the Chk1 inhibitor PF-00477736 as a docetaxel-sensitizing agent...
  8. ncbi Regulation of Chk1 includes chromatin association and 14-3-3 binding following phosphorylation on Ser-345
    Kecheng Jiang
    Department of Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, Ohio 45267 0524, USA
    J Biol Chem 278:25207-17. 2003
    ..The conserved checkpoint kinase Chk1 regulates mitotic progression in response to DNA damage and replication interference by blocking the activation of ..
  9. pmc TAp73 induction by nitric oxide: regulation by checkpoint kinase 1 (CHK1) and protection against apoptosis
    Ali Tebbi
    Universite Paris Sud, Institute of Molecular and Cellular Biochemistry and Biophysics, UMR 8619, F 91405 Orsay, France
    J Biol Chem 286:7873-84. 2011
    ..NO also up-regulated TAp73 mRNA expression, suggesting a transcriptional regulation. The checkpoint kinases Chk1 and Chk2 can regulate TAp73 induction after DNA damage...
  10. doi HY-1 induces G(2)/M cell cycle arrest in human colon cancer cells through the ATR-Chk1-Cdc25C and Weel pathways
    Yu Zhao
    Institute of Nautical Medicine, Nantong University, Nantong, China
    Cancer Sci 104:1062-6. 2013
    ..Our results showed that cdc2 phosphorylation and decreased cdc2 kinase acitivity through the ATR-Chk1-Cdc25C and Weel pathways were the central mechanisms for G2 /M phase arrest in human colon cancer cells.
  11. doi Identification of XAF1 as a novel cell cycle regulator through modulating G(2)/M checkpoint and interaction with checkpoint kinase 1 in gastrointestinal cancer
    Jide Wang
    Department of Digestive Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China
    Carcinogenesis 30:1507-16. 2009
    ..The aim of this study is to elucidate the mechanism of XAF1 in regulating cell growth...
  12. doi Inhibition of checkpoint kinase 1 abrogates G2/M checkpoint activation and promotes apoptosis under heat stress
    Yukihiro Furusawa
    Department of Radiological Sciences, Life Science Research Center, Graduate School of Medicine Pharmaceutical Sciences, University of Toyama, Sugitani, Toyama, Japan
    Apoptosis 17:102-12. 2012
    ..Here, we demonstrated a novel evidence that checkpoint kinase 1 (Chk1) plays crucial roles in the apoptosis and regulation of cell cycle progression in cells under HS...
  13. ncbi Interaction of checkpoint kinase 1 and the X-linked inhibitor of apoptosis during mitosis
    V Galvan
    Buck Institute for Age Research, 8001 Redwood Blvd, Novato, CA 94945, USA
    FEBS Lett 558:57-62. 2004
    We report here that the checkpoint kinase Chk1 and the inhibitor of apoptosis protein (IAP) family member XIAP can be found in a complex in association with condensed chromosomes aligned at the metaphase plate during mitosis...
  14. ncbi Chaperoning checkpoint kinase 1 (Chk1), an Hsp90 client, with purified chaperones
    Sonnet J H Arlander
    Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Graduate School
    J Biol Chem 281:2989-98. 2006
    Checkpoint kinase 1 (Chk1), a serine/threonine kinase that regulates DNA damage checkpoints, is destabilized when heat shock protein 90 (Hsp90) is inhibited, suggesting that Chk1 is an Hsp90 client...
  15. pmc Chk1-mediated phosphorylation of FANCE is required for the Fanconi anemia/BRCA pathway
    XiaoZhe Wang
    Department of Radiation Oncology, Dana Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA
    Mol Cell Biol 27:3098-108. 2007
    ..Here, we show that, in response to DNA damage, Chk1 directly phosphorylates the FANCE subunit of the FA core complex on two conserved sites (threonine 346 and serine ..
  16. pmc DNA methylation inhibitor 5-Aza-2'-deoxycytidine induces reversible genome-wide DNA damage that is distinctly influenced by DNA methyltransferases 1 and 3B
    Stela S Palii
    Department of Biochemistry and Molecular Biology, University of Florida, College of Medicine, Box 100245, 1600 SW Archer Rd, Gainesville, FL 32610, USA
    Mol Cell Biol 28:752-71. 2008
    ..revealed activation of key strand break repair proteins including ATM, ATR (ATM-Rad3-related), checkpoint kinase 1 (CHK1), BRCA1, NBS1, and RAD51 by Western blotting and immunofluorescence...
  17. doi Knock-down of human MutY homolog (hMYH) decreases phosphorylation of checkpoint kinase 1 (Chk1) induced by hydroxyurea and UV treatment
    Soo Hyun Hahm
    Department of Advanced Technology Fusion, Konkuk University, Seoul, Korea
    BMB Rep 44:352-7. 2011
    ..hMYH-disrupted cells decreased the phosphorylation of Chk1 upon HU or UV treatment and increased the phosphorylation of Cdk2 and the amount of Cdc25A, but not Cdc25C...
  18. ncbi Characterization of the 5'flanking region of the human Chk1 gene: identification of E2F1 functional sites
    Laura Carrassa
    Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Cell Cycle 2:604-9. 2003
    b>Chk1 kinase is a key signal transducer in the checkpoint pathways responding to DNA damage. Chk1 has been shown to be transcriptionally down-regulated in response to cis-dichloro-diamino platinum treatment in a p53-dependent manner...
  19. pmc Functional interaction between BLM helicase and 53BP1 in a Chk1-mediated pathway during S-phase arrest
    Sagar Sengupta
    Laboratory of Human Carcinogenesis, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Cell Biol 166:801-13. 2004
    ..The active Chk1 kinase was essential for both the accurate focal colocalization of 53BP1 with BLM and the consequent stabilization ..
  20. pmc Tethering DNA damage checkpoint mediator proteins topoisomerase IIbeta-binding protein 1 (TopBP1) and Claspin to DNA activates ataxia-telangiectasia mutated and RAD3-related (ATR) phosphorylation of checkpoint kinase 1 (Chk1)
    Laura A Lindsey-Boltz
    Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599 7260, USA
    J Biol Chem 286:19229-36. 2011
    ..upon exposure to ultraviolet light by phosphorylating many effector proteins including the checkpoint kinase Chk1. The conventional view of ATR activation involves a universal signal consisting of genomic regions of replication ..
  21. doi Novel regulation of checkpoint kinase 1: Is checkpoint kinase 1 a good candidate for anti-cancer therapy?
    Hidemasa Goto
    Division of Biochemistry, Aichi Cancer left Research Institute, Nagoya, Japan
    Cancer Sci 103:1195-200. 2012
    ..to genetic defect(s) in the ATM (ataxia-telangiectasia mutated)-Chk2-p53 pathway, an ATR (ATM- and Rad3-related)-Chk1-Cdc25 route is the sole checkpoint pathway in a majority of cancer cells...
  22. pmc Kinase-independent function of checkpoint kinase 1 (Chk1) in the replication of damaged DNA
    Juliana Speroni
    Cell Cycle and Genomic Stability Laboratory, Fundación Instituto Leloir Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Universidad de Buenos Aires, C1405BWE Buenos Aires, Argentina
    Proc Natl Acad Sci U S A 109:7344-9. 2012
    The checkpoint kinases Chk1 and ATR are broadly known for their role in the response to the accumulation of damaged DNA...
  23. pmc Reconstitution of a human ATR-mediated checkpoint response to damaged DNA
    Jun Hyuk Choi
    Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, NC 27599 7260, USA
    Proc Natl Acad Sci U S A 104:13301-6. 2007
    ..ATR in the presence of topoisomerase II binding protein 1 (TopBP1) mediator/adaptor protein phosphorylates the Chk1 signal-transducing kinase in a reaction that is strongly dependent on the presence of DNA containing bulky base ..
  24. doi Interaction with checkpoint kinase 1 modulates the recruitment of nucleophosmin to chromatin
    Songbi Chen
    Manchester Interdisciplinary Biocentre, University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom
    J Proteome Res 8:4693-704. 2009
    The Checkpoint kinase 1 (Chk1) plays a central role in the cellular response to DNA damage and also contributes to the efficacy of DNA replication in the absence of genomic stress...
  25. pmc Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R
    Ge Li
    Department of Pathology, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, USA
    Retrovirology 7:59. 2010
    ..Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive...
  26. doi Involvement of the role of Chk1 in lithium-induced G2/M phase cell cycle arrest in hepatocellular carcinoma cells
    Xiao Ming Wang
    Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, 130 Dong an Road, Shanghai 200032, China
    J Cell Biochem 104:1181-91. 2008
    ..Checkpoint kinase 1 (Chk1), a critical enzyme in DNA damage-induced G2/M arrest, was at least partially responsible for the lithium action...
  27. ncbi Checkpoint kinase 1-mediated phosphorylation of Cdc25C and bad proteins are involved in antitumor effects of loratadine-induced G2/M phase cell-cycle arrest and apoptosis
    Jinn Shiun Chen
    Department of Surgery, Division of Colon and Rectal Surgery, Chang Gung Memorial Hospital, Linkou, Taiwan
    Mol Carcinog 45:461-78. 2006
    ..that the LOR-induced Cdc25C (Ser-216) phosphorylation was blocked in the presence of checkpoint kinase 1 (Chk1) specific inhibitor (SB-218078)...
  28. ncbi Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint
    Tiziana Bruno
    Experimental Chemotherapy Laboratory, Department of Experimental Oncology, Regina Elena Cancer Institute, 00158 Rome, Italy
    Cancer Cell 10:473-86. 2006
    ..Notably, Che-1 contributes to the maintenance of the G2/M checkpoint induced by DNA damage. These findings identify a mechanism by which checkpoint kinases regulate responses to DNA damage...
  29. doi Checkpoint kinase 1 down-regulation by an inducible small interfering RNA expression system sensitized in vivo tumors to treatment with 5-fluorouracil
    Monica Ganzinelli
    Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
    Clin Cancer Res 14:5131-41. 2008
    ..To better investigate the role of checkpoint kinase 1 (Chk1) in cellular response to different anticancer agents, Chk1 was knocked down in HCT-116 cell line and in its p53-..
  30. ncbi The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation
    P Chen
    Agouron Pharmaceuticals, Inc San Diego, California 92121, USA
    Cell 100:681-92. 2000
    The checkpoint kinase Chk1 is an important mediator of cell cycle arrest following DNA damage. The 1...
  31. pmc Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint
    Q Liu
    Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA
    Genes Dev 14:1448-59. 2000
    b>Chk1, an evolutionarily conserved protein kinase, has been implicated in cell cycle checkpoint control in lower eukaryotes...
  32. pmc Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints
    Hui Zhao
    Department of Cell Biology and Physiology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8228, 660 South Euclid Avenue, St Louis, MO 63110 1093, USA
    Proc Natl Acad Sci U S A 99:14795-800. 2002
    ..In mice, Chk1 provides an essential function in the absence of environmentally imposed genotoxic stress...
  33. ncbi Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on Ser-317 in response to ionizing radiation
    Magtouf Gatei
    Queensland Institute of Medical Research, Post Office Royal Brisbane Hospital, Brisbane, Queensland 4029, Australia
    J Biol Chem 278:14806-11. 2003
    ..The checkpoint functions of ATR and ATM are mediated, in part, by a pair of checkpoint effector kinases termed Chk1 and Chk2...
  34. pmc Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA
    Viola Ellison
    Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA
    PLoS Biol 1:E33. 2003
    ....
  35. pmc MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation
    Yi Wang
    Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 100:15387-92. 2003
    ..with the ATR (ATM- and Rad3-related) kinase to form a signaling module and regulate the phosphorylation of Chk1 and SMC1 (structure maintenance of chromosome 1)...
  36. ncbi Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase
    Alwin Krämer
    Danish Cancer Society, Institute of Cancer Biology, Department of Cell Cycle and Cancer, Strandboulevarden 49, DK 2100 Copenhagen Ø, Denmark
    Nat Cell Biol 6:884-91. 2004
    ..Here, we show that human Chk1 kinase localizes to interphase, but not mitotic, centrosomes...
  37. ncbi Chk1 is essential for tumor cell viability following activation of the replication checkpoint
    Song H Cho
    Department of Discovery Research, DNAX Research Incorporated, Palo Alto, California, USA
    Cell Cycle 4:131-9. 2005
    b>Chk1 (checkpoint kinase 1) is an evolutionarily conserved serine/threonine kinase involved in DNA damage responses...
  38. pmc Methylator-induced, mismatch repair-dependent G2 arrest is activated through Chk1 and Chk2
    Aaron W Adamson
    Department of Biochemistry and Molecular Biology and the Stanley S Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA
    Mol Biol Cell 16:1513-26. 2005
    ..Here, we show that MNNG exposure results in activation of the cell cycle checkpoint kinases ATM, Chk1, and Chk2, each of which has been implicated in the triggering of the G2/M checkpoint response...
  39. ncbi The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair
    Claus Storgaard Sørensen
    Danish Cancer Society, Institute of Cancer Biology, DK 2100 Copenhagen, Denmark
    Nat Cell Biol 7:195-201. 2005
    The essential checkpoint kinase Chk1 is required for cell-cycle delays after DNA damage or blocked DNA replication. However, it is unclear whether Chk1 is involved in the repair of damaged DNA...
  40. ncbi Depletion of Chk1 leads to premature activation of Cdc2-cyclin B and mitotic catastrophe
    Hiroyuki Niida
    Department of Biochemistry and Cell Biology, Nagoya City University, 1 Kawasumi, Mizuho cho, Mizuho ku, Nagoya 467 8601, Japan
    J Biol Chem 280:39246-52. 2005
    ..We demonstrate here the essential role of the ATM/ATR-p53 pathway in mitotic catastrophe from premature mitosis. Chk1 deficiency resulted in a premature onset of mitosis because of abnormal activation of cyclin B-Cdc2 and led to the ..
  41. pmc Chk1 and p21 cooperate to prevent apoptosis during DNA replication fork stress
    Rene Rodriguez
    Institute for Cancer Studies, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield S10 2RX, United Kingdom
    Mol Biol Cell 17:402-12. 2006
    ..potent inducers of death in S-phase cells upon small interfering RNA-mediated depletion of the checkpoint kinase Chk1. This death response is independent of p53 and Chk2...
  42. pmc Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation
    Shizhou Liu
    Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Mol Cell Biol 26:6056-64. 2006
    TopBP1 and Claspin are adaptor proteins that facilitate phosphorylation of Chk1 by the ATR kinase in response to genotoxic stress...
  43. ncbi Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1 and mediate Claspin function
    Claudia C S Chini
    Department of Oncology Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
    J Biol Chem 281:33276-82. 2006
    Claspin is a checkpoint protein involved in ATR (ataxia telangiectasia mutated- and Rad3-related)-dependent Chk1 activation in Xenopus and human cells...
  44. ncbi The E2F-regulated gene Chk1 is highly expressed in triple-negative estrogen receptor /progesterone receptor /HER-2 breast carcinomas
    Lieve Verlinden
    Laboratorium voor Experimentele Geneeskunde en Endocrinologie and CMPG ESAT, Katholieke Universiteit Leuven, Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium
    Cancer Res 67:6574-81. 2007
    We previously showed that checkpoint kinase 1 (Chk1) and Claspin, two DNA-damage checkpoint proteins, were down-regulated by 1,25-dihydroxyvitamin D(3), a known inhibitor of cell proliferation...
  45. doi Chk1 and Chk2 are differentially involved in homologous recombination repair and cell cycle arrest in response to DNA double-strand breaks induced by camptothecins
    Min Huang
    Division of Anti tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhangjiang Hi Tech Park, Shanghai 201203, Peoples Republic of China
    Mol Cancer Ther 7:1440-9. 2008
    ..In this process, both checkpoint kinases 1 and 2 (Chk1 and Chk2, respectively) are activated, but their differential roles, especially in the coordination of checkpoint ..
  46. pmc Essential function of Chk1 can be uncoupled from DNA damage checkpoint and replication control
    Deborah Wilsker
    Department of Radiation Oncology and Molecular Radiation Sciences and The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA
    Proc Natl Acad Sci U S A 105:20752-7. 2008
    b>Chk1 is widely known as a DNA damage checkpoint signaling protein. Unlike many other checkpoint proteins, Chk1 also plays an essential but poorly defined role in the proliferation of unperturbed cells...
  47. pmc The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity to replication stress
    You Wei Zhang
    Department of Pharmacology, Case Comprehensive Caner Center, School of Medicine, Case Western Reserve University, 2109 Adelbert Road, Wood Building W343A, Cleveland, OH 44106, USA
    Mol Cell 35:442-53. 2009
    ATR and Chk1 are two key protein kinases in the replication checkpoint. Activation of ATR-Chk1 has been extensively investigated, but checkpoint termination and replication fork restart are less well understood...
  48. doi Constitutive activation of the DNA damage signaling pathway in acute myeloid leukemia with complex karyotype: potential importance for checkpoint targeting therapy
    Cindy Cavelier
    Universite de Toulouse, LBCMCP, Centre National de la Recherche Scientifique, LBCMCP UMR5088, Toulouse, France
    Cancer Res 69:8652-61. 2009
    ..We show that antagonizing CHK1 kinase with a small inhibitory compound or by RNA interference strongly reduces the clonogenic properties of high-..
  49. pmc Enhanced H2AX phosphorylation, DNA replication fork arrest, and cell death in the absence of Chk1
    Mary E Gagou
    Institute for Cancer Studies, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
    Mol Biol Cell 21:739-52. 2010
    ..enhanced in response to replication inhibitors but not ionizing radiation in HCT116 or SW480 cells depleted of Chk1. Although H2AX phosphorylation precedes the induction of apoptosis in such cells, our results suggest that cells ..
  50. pmc 14-3-3gamma mediates Cdc25A proteolysis to block premature mitotic entry after DNA damage
    Kousuke Kasahara
    Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan
    EMBO J 29:2802-12. 2010
    ..of 14-3-3 (beta and zeta isoforms in mammalian cells and Rad24 in fission yeast) bind to Ser345-phosphorylated Chk1 and promote its nuclear retention...
  51. doi USP7 regulates the stability and function of HLTF through deubiquitination
    Peng Qing
    Department of Respiratory Diseases, Minhang District Central Hospital, Shanghai, P R China
    J Cell Biochem 112:3856-62. 2011
    ..Thus, our results delineate a previously unknown USP7-HLTF-PCNA molecular network controlling DNA damage response...
  52. ncbi Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25
    Y Sanchez
    Verna and Marrs McLean Department of Biochemistry, Howard Hughes Medical Institute, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Science 277:1497-501. 1997
    ..A human gene was identified that encodes the protein Chk1, a homolog of the Schizosaccharomyces pombe Chk1 protein kinase, which is required for the DNA damage checkpoint...
  53. ncbi Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216
    C Y Peng
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Science 277:1501-5. 1997
    ..b>Chk1, a fission yeast kinase involved in the DNA damage checkpoint response, phosphorylated Cdc25C in vitro on serine-..
  54. pmc The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites
    S Y Shieh
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Genes Dev 14:289-300. 2000
    ..that a S20 kinase activity copurifies with the human homolog of the Schizosaccharomyces pombe checkpoint kinase, Chk1 (hCHK1)...
  55. ncbi The Chk1 protein kinase and the Cdc25C regulatory pathways are targets of the anticancer agent UCN-01
    P R Graves
    Department of Cell Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 275:5600-5. 2000
    ..The checkpoint kinases, Chk1 and Cds1, are proposed to regulate the interactions between human Cdc25C and 14-3-3 proteins by phosphorylating ..
  56. ncbi The many substrates and functions of ATM
    M B Kastan
    Department of Hematology Oncology, Saint Jude Children s Research Hospital, D1034, 332 North Lauderdale Street, Memphis, Tennessee 38105, USA
    Nat Rev Mol Cell Biol 1:179-86. 2000
    ..Although it is hard to understand how a single gene product is involved in so many physiological processes, a clear picture is starting to emerge...
  57. pmc ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1
    H Zhao
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110 1093, USA
    Mol Cell Biol 21:4129-39. 2001
    b>Chk1 is an evolutionarily conserved protein kinase that regulates cell cycle progression in response to checkpoint activation...
  58. pmc Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing
    C Feijoo
    Division of Cell Signaling, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom
    J Cell Biol 154:913-23. 2001
    ..Here we describe evidence for the participation of Chk1 in an intra-S phase checkpoint in mammalian cells...
  59. ncbi BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage
    Ronit I Yarden
    Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Genet 30:285-9. 2002
    ..Here we show that BRCA1 is essential for activating the Chk1 kinase that regulates DNA damage-induced G2/M arrest...
  60. ncbi A role for PI 3-kinase and PKB activity in the G2/M phase of the cell cycle
    Emma Shtivelman
    Cancer Research Institute, University of California San Francisco, San Francisco, CA 94143 0128, USA
    Curr Biol 12:919-24. 2002
    ..Inhibition of PI 3-kinase results in activation of Chk1, whereas caPKB inhibits the ability of Chk1 to become activated in response to treatment with hydroxyurea...
  61. ncbi Structural basis for Chk1 inhibition by UCN-01
    Baoguang Zhao
    Department of Structural Biology, GlaxoSmithKline, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 277:46609-15. 2002
    b>Chk1 is a serine-threonine kinase that plays an important role in the DNA damage response, including G(2)/M cell cycle control...
  62. ncbi Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A
    Claus Storgaard Sørensen
    Danish Cancer Society, Institute of Cancer Biology, Strandboulevarden 49, DK 2100 Copenhagen Ø, Denmark
    Cancer Cell 3:247-58. 2003
    b>Chk1 kinase coordinates cell cycle progression and preserves genome integrity...
  63. ncbi Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents
    Zhan Xiao
    Cancer Research, Abbott Laboratories, Abbott Park, Illinois 60064 6101, USA
    J Biol Chem 278:21767-73. 2003
    ..and Lukas J. (2001) Nature 410, 842-847). The degradation of Cdc25A is abrogated by caffeine, which implicates Chk1 as the potential mediator (Mailand, N., Falck, J., Lukas, C., Syljuasen, R. G., Welcker, M., Bartek, J...
  64. ncbi Activation of the ATR-mediated DNA damage response by the HIV-1 viral protein R
    Mikhail Roshal
    Department of Microbiology and Immunology, University of Rochester Cancer Center, Rochester, New York 14642, USA
    J Biol Chem 278:25879-86. 2003
    ..As with DNA damage, activation of ATR by Vpr results in phosphorylation of Chk1. This study provides conclusive evidence of activation of the ATR-initiated DNA damage-signaling pathway by a viral ..
  65. ncbi Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex
    Dawn Marie Goudelock
    Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267 0524, USA
    J Biol Chem 278:29940-7. 2003
    ..The conserved checkpoint kinase, Chk1, regulates mitotic progression in response to DNA damage by blocking the activation of Cdk1/cyclin B...
  66. ncbi Human claspin is required for replication checkpoint control
    Claudia Christiano Silva Chini
    Department of Oncology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA
    J Biol Chem 278:30057-62. 2003
    Claspin is a newly identified protein that regulates Chk1 activation in Xenopus. In the present study we investigated the role of human Claspin in the DNA damage/replication checkpoint in mammalian cells...
  67. pmc Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding
    Mei Shya Chen
    Howard Hughes Medical Institute, Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110 1093, USA
    Mol Cell Biol 23:7488-97. 2003
    The order and fidelity of cell cycle events in mammals is intimately linked to the integrity of the Chk1 kinase-Cdc25A phosphatase pathway...
  68. ncbi Lack of PTEN sequesters CHK1 and initiates genetic instability
    Janusz Puc
    Institute for Cancer Genetics, Columbia University, New York, New York 10032, USA
    Cancer Cell 7:193-204. 2005
    ..The checkpoint defect was traced to the ability of AKT to phosphorylate CHK1 at serine 280, since a nonphosphorylated mutant of CHK1 (S280A) complemented the checkpoint defect and restored ..
  69. pmc ATRIP binding to replication protein A-single-stranded DNA promotes ATR-ATRIP localization but is dispensable for Chk1 phosphorylation
    Heather L Ball
    Department of Biochemistry, Vanderbilt University, Nashville, TN 37232, USA
    Mol Biol Cell 16:2372-81. 2005
    ..the ATRIP-RPA-ssDNA interaction is not absolutely essential for ATR activation because ATR phosphorylates Chk1 in cells expressing only a mutant of ATRIP that does not bind to RPA-ssDNA...
  70. pmc Inhibition of human Chk1 causes increased initiation of DNA replication, phosphorylation of ATR targets, and DNA breakage
    Randi G Syljuåsen
    Institute of Cancer Biology, Department of Cell Cycle and Cancer, Danish Cancer Society, Strandboulevarden 49, 2100 Copenhagen, Denmark
    Mol Cell Biol 25:3553-62. 2005
    Human checkpoint kinase 1 (Chk1) is an essential kinase required to preserve genome stability...
  71. ncbi Genotoxic stress targets human Chk1 for degradation by the ubiquitin-proteasome pathway
    You Wei Zhang
    Signal Transduction Program, The Burnham Institute, La Jolla, California 92037, USA
    Mol Cell 19:607-18. 2005
    The Chk1 kinase is a major effector of S phase checkpoint signaling during the cellular response to genotoxic stress. Here, we report that replicative stress induces the polyubiquitination and degradation of Chk1 in human cells...
  72. pmc Activation of the ATR pathway by human immunodeficiency virus type 1 Vpr involves its direct binding to chromatin in vivo
    Maoyi Lai
    Division of Oncology Research, Mayo Clinic, Guggenheim 1342, Rochester, MN 55905, USA
    J Virol 79:15443-51. 2005
    ..of Vpr does not cause DNA double-strand breaks but rather induces ATR activation, as indicated by induction of Chk1 phosphorylation and the formation of gamma-H2AX and 53BP1 nuclear foci...
  73. pmc Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase
    Eva Petermann
    Genome Damage and Stability Centre, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ, UK
    Mol Cell Biol 26:3319-26. 2006
    b>Chk1 protein kinase maintains replication fork stability in metazoan cells in response to DNA damage and DNA replication inhibitors...
  74. ncbi Regulation of mitotic function of Chk1 through phosphorylation at novel sites by cyclin-dependent kinase 1 (Cdk1)
    Takashi Shiromizu
    Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, Aichi 464 8681, Japan
    Genes Cells 11:477-85. 2006
    b>Chk1 is phosphorylated at Ser317 and Ser345 by ATR in response to stalled replication and genotoxic stresses. This Chk1 activation is thought to play critical roles in the prevention of premature mitosis...
  75. ncbi Depletion of CHK1, but not CHK2, induces chromosomal instability and breaks at common fragile sites
    S G Durkin
    Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109, USA
    Oncogene 25:4381-8. 2006
    ..fragile site stability, we have investigated the effects of depletion of the cell cycle checkpoint kinases, CHK1 and CHK2 on common fragile site stability in human cells...
  76. ncbi Regulation of mitotic entry by microcephalin and its overlap with ATR signalling
    Gemma K Alderton
    Genome Damage and Stability Centre, University of Sussex, East Sussex, BN1 9RQ, UK
    Nat Cell Biol 8:725-33. 2006
    ..MCPH1 have implicated the protein it encodes as a DNA-damage response protein that regulates the transcription of Chk1 and BRCA1, two genes involved in the response to DNA damage...
  77. pmc Checkpoint kinase 1 (Chk1) is required for mitotic progression through negative regulation of polo-like kinase 1 (Plk1)
    Jiabin Tang
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 103:11964-9. 2006
    Although the essential function of checkpoint kinase 1 (Chk1) in DNA damage response has been well established, the role of Chk1 in normal cell cycle progression is unclear...
  78. ncbi CHK1 phosphorylates CDC25B during the cell cycle in the absence of DNA damage
    Estelle Schmitt
    LBCMCP CNRS UMR5088, IFR109, Universite Paul Sabatier, 118 route de Narbonne, 31062 Toulouse, France
    J Cell Sci 119:4269-75. 2006
    ..Centrosome-associated checkpoint kinase 1 (CHK1) has been proposed to contribute to the proper timing of a normal cell division cycle by inhibiting the activation ..
  79. pmc Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit
    Van Leung-Pineda
    Department of Cell Biology and Physiology and Howard Hughes Medical Institute, Washington University School of Medicine, Box 8228, 660 South Euclid Ave, St Louis, MO 63110, USA
    Mol Cell Biol 26:7529-38. 2006
    In higher eukaryotic organisms, the checkpoint kinase 1 (Chk1) contributes essential functions to both cell cycle and checkpoint control...
  80. ncbi Phosphatase type 2A-dependent and -independent pathways for ATR phosphorylation of Chk1
    Ge Li
    Department of Pathology, Department of Microbiology Immunology, Institute of Human Virology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA
    J Biol Chem 282:7287-98. 2007
    ..that, when activated by hydroxyurea, UV, or human immunodeficiency virus-1 Vpr, causes cell cycle arrest through Chk1-Ser(345) phosphorylation...
  81. ncbi Chk1 is required for spindle checkpoint function
    George Zachos
    Beatson Institute for Cancer Research, Garscube Estate, Switchback Road, Glasgow G61 1BD, United Kingdom
    Dev Cell 12:247-60. 2007
    The spindle checkpoint delays anaphase onset in cells with mitotic spindle defects. Here, we show that Chk1, a component of the DNA damage and replication checkpoints, protects vertebrate cells against spontaneous chromosome ..
  82. pmc p53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage
    H Christian Reinhardt
    Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, E18 580, Cambridge, MA 02139, USA
    Cancer Cell 11:175-89. 2007
    In response to DNA damage, eukaryotic cells activate ATM-Chk2 and/or ATR-Chk1 to arrest the cell cycle and initiate DNA repair...
  83. pmc Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage
    Yasumichi Inoue
    Radiobiology Division, National Cancer Center Research Institute, Tokyo, Japan
    EMBO J 26:2083-93. 2007
    ..However, the phosphorylation of pRB at Ser612 was conducted by Chk1/2 after DNA damage, and inhibition of ATM-Chk1/2 activity suppressed the phosphorylation of Ser612 and the binding ..
  84. pmc Chk1 regulates the density of active replication origins during the vertebrate S phase
    Apolinar Maya-Mendoza
    Faculty of Life Sciences, University of Manchester, MIB, Manchester, UK
    EMBO J 26:2719-31. 2007
    The checkpoint kinase 1 (Chk1) preserves genome integrity when replication is performed on damaged templates. Recently, Chk1 has also been implicated in regulating different aspects of unperturbed S phase...
  85. ncbi ATR pathway is the primary pathway for activating G2/M checkpoint induction after re-replication
    Jie Jessie Lin
    Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, Virginia 22908, USA
    J Biol Chem 282:30357-62. 2007
    ..ATM kinase and the Mre11-Rad50-Nbs1 complex do not appear to play significant roles in the checkpoint. Chk1 activation occurs at early stages, whereas Chk2 activation occurs much later...
  86. ncbi The regulatory beta-subunit of protein kinase CK2 accelerates the degradation of CDC25A phosphatase through the checkpoint kinase Chk1
    Jan Kreutzer
    Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK 5230 Odense, Denmark
    Int J Oncol 31:1251-9. 2007
    ..b>Chk1 has been shown to phosphorylate CDC25 family members down-regulating their phosphatase activity through distinct ..
  87. ncbi Loss of CHK1 function impedes DNA damage-induced FANCD2 monoubiquitination but normalizes the abnormal G2 arrest in Fanconi anemia
    Jean Hugues Guervilly
    Equipe voie FANC BRCA et Cancer, CNRS FRE2939, CEA LRC43V, Univ Paris Sud, Institut Gustave Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France
    Hum Mol Genet 17:679-89. 2008
    ..Moreover, we demonstrate that CHK1 and its interacting partner CLASPIN that act downstream in the ATR pathway are required for both FANCD2 ..
  88. doi Apoptosis induced by replication inhibitors in Chk1-depleted cells is dependent upon the helicase cofactor Cdc45
    R Rodriguez
    Institute for Cancer Studies, University of Sheffield, School of Medicine and Biomedical Sciences, Sheffield S10 2RX, UK
    Cell Death Differ 15:889-98. 2008
    Checkpoint kinase 1 (Chk1) responds to disruption of DNA replication to maintain the integrity of stalled forks, promote homologous recombination-mediated repair of replication fork lesions, and control inappropriate firing of replication ..
  89. doi Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced transcriptional repression
    Midori Shimada
    Department of Cell Biology and Biochemistry, Graduate School of Medical Sciences, Nagoya City University, 1 Kawasumi, Mizuho cho, Mizuho ku, Nagoya 467 8601, Japan
    Cell 132:221-32. 2008
    ..H3-T11 phosphorylation occurs throughout the cell cycle and is Chk1 dependent in vivo...
  90. pmc Expanded roles for Chk1 in genome maintenance
    Greg H Enders
    Department of Medicine, Fox Chase Cancer Center, Philadelphia, PA 19111, USA
    J Biol Chem 283:17749-52. 2008
    b>Chk1 is a conserved kinase that imposes cell cycle delays in response to impediments to DNA replication...
  91. pmc Chk1 and Claspin potentiate PCNA ubiquitination
    Xiaohong H Yang
    Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA
    Genes Dev 22:1147-52. 2008
    b>Chk1 is a kinase crucial for genomic integrity and an effector of ATR (ATM and Rad3-related) in DNA damage response...
  92. ncbi DNA damage-induced S phase arrest in human breast cancer depends on Chk1, but G2 arrest can occur independently of Chk1, Chk2 or MAPKAPK2
    Wen Hui Zhang
    Department of Pharmacology and Toxicology, and the Norris Cotton Cancer Center, Dartmouth Medical School, Lebanon, New Hampshire 03756, USA
    Cell Cycle 7:1668-77. 2008
    Checkpoint kinases Chk1 and Chk2 are two key components in the DNA damage-activated checkpoint signaling pathways...
  93. doi Cleavage-mediated activation of Chk1 during apoptosis
    Kenkyo Matsuura
    Laboratory of Human Molecular Genetics, Graduate School of Natural Science and Technology, Kanazawa University, Kakuma machi, Kanazawa, Japan
    J Biol Chem 283:25485-91. 2008
    The Chk1 kinase is highly conserved from yeast to humans and is well known to function in the cell cycle checkpoint induced by genotoxic or replication stress...
  94. doi Chk1 phosphorylation at Ser286 and Ser301 occurs with both stalled DNA replication and damage checkpoint stimulation
    Yosuke Ikegami
    Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, Aichi 464 8681, Japan
    Biochem Biophys Res Commun 377:1227-31. 2008
    We previously reported Chk1 to be phosphorylated at Ser286 and Ser301 by cyclin-dependent kinase (Cdk) 1 during mitosis [T. Shiromizu et al., Genes Cells 11 (2006) 477-485]...
  95. doi Common single-nucleotide polymorphisms in DNA double-strand break repair genes and breast cancer risk
    Karen A Pooley
    Cancer Research UK Genetic Epidemiology Unit, Strangeways Research Laboratory, Worts Causeway, Cambridge CB1 8RN, United Kingdom
    Cancer Epidemiol Biomarkers Prev 17:3482-9. 2008
    ..20; 95% CI, 1.07-1.36; P trend = 0.002). In summary, there was little evidence of breast cancer susceptibility with any of the SNPs studied, but larger studies would be needed to confirm subgroup effects...
  96. pmc ATR and Chk1 suppress a caspase-3-dependent apoptotic response following DNA replication stress
    Katie Myers
    Institute for Cancer Studies, School of Medicine and Biomedical Sciences, University of Sheffield, Sheffield, United Kingdom
    PLoS Genet 5:e1000324. 2009
    ..Much less is known about the control of apoptosis following DNA replication stress. Recent work indicates that Chk1, the downstream phosphorylation target of ATR, protects cells from apoptosis induced by DNA replication inhibitors ..
  97. ncbi Replication stress activates DNA polymerase alpha-associated Chk1
    Lorena Taricani
    Discovery Research, Schering Plough Biopharma, Palo Alto, California 94304 1104, USA
    Cell Cycle 8:482-9. 2009
    b>Chk1 contributes to both intra-S and DNA damage checkpoint responses...
  98. pmc Claspin and Chk1 regulate replication fork stability by different mechanisms
    Jennifer Scorah
    Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA
    Cell Cycle 8:1036-43. 2009
    The checkpoint mediator protein Claspin facilitates the phosphorylation and activation of Chk1 by ATR and thus is required for efficient DNA replication...
  99. pmc A role for Chk1 in blocking transcriptional elongation of p21 RNA during the S-phase checkpoint
    Rachel Beckerman
    Department of Biological Sciences, Columbia University, New York, New York 10027, USA
    Genes Dev 23:1364-77. 2009
    ..Here we show that ablation of the protein kinase Chk1 rescues the p21 transcription elongation defect when cells are blocked in S phase, as measured by increases in both ..
  100. pmc Novel positive feedback loop between Cdk1 and Chk1 in the nucleus during G2/M transition
    Masato Enomoto
    Division of Biochemistry, Aichi Cancer Center Research Institute, Nagoya, Aichi 464 8681, Japan
    J Biol Chem 284:34223-30. 2009
    b>Chk1, one of the critical transducers in DNA damage/replication checkpoints, prevents entry into mitosis through inhibition of Cdk1 activity. However, it has remained unclear how this inhibition is cancelled at the G(2)/M transition...
  101. doi DNA damage induces Chk1-dependent threonine-160 phosphorylation and activation of Cdk2
    E Bourke
    Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, Galway, Ireland
    Oncogene 29:616-24. 2010
    ..Cdk2 controls normal centrosome duplication, but Chk1-dependent centrosome amplification also occurs after DNA damage...

Research Grants64

  1. Jac A Nickoloff; Fiscal Year: 2016
    ..Recent studies demonstrate that Metnase and DNA-PK (along with replication protein A (RPA), ATM/ATR, Chk1, and others) also function in checkpoint activation and replication stress recovery...
  2. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
    ..canonical protein kinase pathways are responsible for arresting the cell cycle in response to damaged DNA - the ATR-Chk1 pathway and the ATM-Chk2 pathway...
  3. Peter M Burgers; Fiscal Year: 2015
    ..with the sensor kinase Mec1 (human ATR), activates Mec1 to phosphorylate downstream targets including Rad53 (human Chk1/2)...
  4. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
    ..through activating a network of molecules including protein kinases ATM/ATR and their targets checkpoint kinases Chk1 and Chk2...
  5. You Wei Zhang; Fiscal Year: 2016
    ..Central to cell cycle checkpoints is a protein kinase, Chk1, which is essential for cell viability and mammalian embryonic development...
  6. Michael B Yaffe; Fiscal Year: 2016
    ..In response to genotoxic stress, cells activate two canonical protein kinase pathways, the ATR-Chk1 pathway, and the ATM-Chk2 pathway...
  7. TONY R HUNTER; Fiscal Year: 2016
    ..The DNA damage response pathway involves activation of a series of protein kinases, including ATM, ATR, and Chk1/Chk2...
  8. Peter M Burgers; Fiscal Year: 2016
    ..A second protein kinase, Rad53, which is related to human Chk1 and Chk2, acts downstream in halting the cell cycle and activating other response pathways...
  9. CELL CYCLE CHECKPOINT CONTROL IN RESPONSE TO DNA DAMAGE
    Nancy C Walworth; Fiscal Year: 2011
    ..Experiments described in this proposal will continue to investigate the protein kinase Chk1, a key regulator of the checkpoint in eukaryotic cells...
  10. DISSECTION OF THE DNA DAMAGE CHECKPOINT PATHWAYS
    Yolanda Sanchez; Fiscal Year: 2009
    ..Thus, checkpoint pathways are being tested for their value as therapeutic targets. The conserved checkpoint kinase Chk1 regulates mitotic progression in response to ionizing radiation, other forms of DNA damage and replication ..
  11. ATF2 in DNA damage response.
    ZE apos EV A RONAI; Fiscal Year: 2010
    ..Furthermore, ATF2 is also required for the activation of ATM, and consequently of Chk1 and Chk2...
  12. CHANGYAN CHEN; Fiscal Year: 2016
    ..In this process, Plk1 was activated in a Chk1-dependent fashion...
  13. Chk1 signaling in the G2 DNA damage checkpoint
    MATTHEW O CONNELL; Fiscal Year: 2009
    ..first renewal of our studies into the control of genome integrity by the G2 DNA damage checkpoint effector kinase, Chk1. DNA damage checkpoints halt cell cycle progression when genomic lesions are detected and thus allow time for DNA ..
  14. Lee Zou; Fiscal Year: 2016
    ..Furthermore, we will investigate how the ATR- Chk1 signaling pathway is activated during the early stage of DNA damage response, and how it is deactivated at the late ..
  15. Wendell G Yarbrough; Fiscal Year: 2016
    ..agents mediated, at least in part, by LZAP abrogation of the G2/M checkpoint through binding and inhibition of Chk1 and Chk2...
  16. Yuko Nakajima; Fiscal Year: 2014
    ..will be analyzed using molecular markers for SAC activity (Mad1 phosphorylation) and for DDC activity (Rad53 and Chk1 phosphorylation)...
  17. Fhit modulation of cell cycle progression and DNA damage response
    Kay Huebner; Fiscal Year: 2010
    ..response andapoptosis associated proteins and that Fhit over-expression modulates expression of Cyclin D1, Hus1, Chk1 jind Akt/mTor/Survivin...
  18. New determinants of the DNA damage response in the fission yeast S. pombe
    MATTHEW J O'CONNELL; Fiscal Year: 2013
    ..All forms of DNA damage activate the DNA damage checkpoint, and through its effector kinase Chk1, the cell cycle is halted such that the lesion can be repaired prior to entry into mitosis...
  19. Paul Nghiem; Fiscal Year: 2014
    ..studies have shown promise for caffeine as an inhibitor of ultraviolet-induced skin cancer by suppressing the ATR/Chk1 pathway required for replication checkpoint function...
  20. Role of TopBP1 partner WDR18 in DNA damage checkpoint and DNA replication
    Shan Yan; Fiscal Year: 2012
    ..Specifically, it is not known how the activated sensor kinase ATR phosphorylates its downstream effector protein Chk1. In addition to the critical roles in DNA replication initiation and DNA replication stress response, TopBP1 plays ..
  21. Raoul Tibes; Fiscal Year: 2016
    ....
  22. Analysis of a DNA Damage-Inducible Checkpoint Complex
    Larry Karnitz; Fiscal Year: 2009
    ..This heterotrimeric clamp-like complex is loaded onto DNA at sites of damage, where it activates the ATR-Chk1 checkpoint signaling pathway...
  23. Determination of regulatory mechanisms for BLM helicase
    Sagar Sengupta; Fiscal Year: 2010
    ..Hence in Module A, I will study the specific role of Chk1-mediated phosphorylation on BLM function(s). The two specific aims of this module are: 1...
  24. Fhit as modulator of Chk1 termination and response to DNA-damaging agents
    JOSHUA SALDIVAR; Fiscal Year: 2012
    ..It was recently proposed that defects in degradation machinery for the Chk1 kinase that signals S/G2 checkpoints, could result in loss of cancer cell sensitivity to certain anticancer drugs...
  25. Resham Bhattacharya; Fiscal Year: 2016
    ..apoptosis will be studied by changes in phosphorylation or localization of different markers including ATM1, ATR, Chk1 and Chk2. Cleavage of Caspase-3, 8, 9 and PARP will also be determined...
  26. MATTHEW MICHAEL; Fiscal Year: 2015
    DESCRIPTION (provided by applicant): The ATR-Chk1 signaling pathway plays crucial roles in cell cycle control and in the cellular response to replication stress...
  27. Wenyi Wei; Fiscal Year: 2016
    ..We found that by controlling Claspin destruction, Cdh1 regulates Chk1 activity and further influences the p53 pathway, implicating a role for Cdh1 in DNA damage repair...
  28. A new role of MEPE/OF45 as a co-factor of CHK1 for DNA damage response
    Ya Wang; Fiscal Year: 2010
    ..time that Matrix extracellular phosphoglycoprotein/osteoblast/osteocyte factor 45 (MEPE/OF45), as a co-factor of CHK1, presents in all dividable human cell lines (tested in our laboratory) to affect cellular response to DNA damage...
  29. INDUCTION OF APOPTOSIS BY HIV-1 VPR
    Vicente Planelles; Fiscal Year: 2010
    ..that induction of G2 arrest and apoptosis require phosphorylation of downstream targets of ATR, such as Chk1, BRCA1 and GADD45a. Therefore, the ATR, kinase represents a key determinant of Vpr-induced pathogenesis...
  30. Meredith A Morgan; Fiscal Year: 2016
    DESCRIPTION (provided by applicant): We have recently shown that small molecule inhibitors of Chk1 abrogate the G2 checkpoint and inhibit HRR (homologous recombination repair) in pancreatic cancer cells...
  31. Wwox and Fhit loss and the DNA damage response in breast cancer subtypes
    Kay Huebner; Fiscal Year: 2013
    ..DNA damage response checkpoint inhibitors in breast cancer in vitro: a) Chk1 and Parp1 inhibitors will be tested for effect on specific breast cancer subtypes in tissue culture;b) Chk1 and ..
  32. Fred Bunz; Fiscal Year: 2015
    ..The effectiveness of targeting distinct upstream and downstream components of the ATR pathway, including Cdk2 and Chk1, will be comparatively evaluated in vitro and in vivo...
  33. EBNA3C and tumor supressors
    Erle S Robertson; Fiscal Year: 2010
    ..We will investigate the phosphorylation status of p53 by kinases which include CyclinA/Cdk2, Chk1, Chk2 and ATM which prevents Mdm2 targeted ubiquitination and test the ability of EBNA3C to modulate the function ..
  34. HDAC6-Selective Inhibitors for Pancreatic Cancer Treatment
    Werner Tueckmantel; Fiscal Year: 2010
    ..In addition, the data indicate that some of these novel HDACIs cause loss of the DNA damage checkpoint kinase, Chk1. It is hypothesized that they can sensitize pancreatic tumor cells to genotoxic agents...
  35. Cooperative roles for Atm and Hus1 in genome maintenance
    Robert Weiss; Fiscal Year: 2009
    ..these pathways is incompletely understood in part because components of the Atr pathway, which also includes Chk1 and the Rad9-Rad1-Hus1 (911) complex, are essential for viability...
  36. JOSEPH VINCENT BONVENTRE; Fiscal Year: 2016
    ..the temporal characteristics of ATM/ATR activation and their downstream effectors (including cyclin D1, ELF4/MEF, CHK1, CHK2, p53 and gH2AX) and relate these findings to the differentiation status of the PTC...
  37. Hiroaki Kiyokawa; Fiscal Year: 2015
    ..In response to DNA damages, CDC25 phosphatases are inactivated by CHK1/2-dependent phosphorylation, forming critical targets of cell cycle checkpoint...
  38. William G Dunphy; Fiscal Year: 2016
    ..ATR phosphorylates the checkpoint effector kinase Chk1 with the assistance of the mediator protein Claspin...
  39. Pumin Zhang; Fiscal Year: 2015
    ..Based on our preliminary results, we propose that DNA damage checkpoint kinase 1 (Chk1) regulates Cdc14B's localization and Cdc14B positively regulates Nek1 to allow efficient DNA damage repair...
  40. Dean E Brenner; Fiscal Year: 2016
    ..for the early detection of pancreatic and colorectal cancer using glycoproteomics methods;3) targeted inhibition of Chk1 as a mechanism to reduce repair of radiation induced damage to pancreatic cancer;and 4) improved treatment of ..
  41. Checkpoint Abrogation and MEK 1/2 Inhibition in Myeloma
    Steven Grant; Fiscal Year: 2013
    The goal of this renewal application is to define the largely unexplored relationship between the ATM/ATR/Chk1 DNA-damage checkpoint machinery and the Src/Ras/Raf/MEK/ERK survival signaling pathway in multiple myeloma (MM) cells, and to ..
  42. KWOK KIN WONG; Fiscal Year: 2016
    ....
  43. Bakhtiar Yamini; Fiscal Year: 2016
    ..Studies will first look upstream up p50 at the Chk1/p50 interaction and then look downstream of p50 at the :B-site DNA sequence In Aim 2, experiments will examine ..
  44. DNA Damage Checkpoints
    Thanos Halazonetis; Fiscal Year: 2005
    ..study the DNA damage checkpoint response (cell cycle arrest, apoptosis, radiosensitivity, activation of ATM, ATR, Chk1, Chk2, p53 and Cdc25C) in cells in which 53BP1 function is upregulated or downregulated...
  45. DNA damage signaling in oxygen toxicity in lung cells
    KUMUDA DAS; Fiscal Year: 2007
    ..transduces hyperoxia-mediated DNA damage signals by activating checkpoint proteins p53 and/or checkpoint kinase1 (Chk1)...
  46. DNA damage response and DDB
    Pradip Raychaudhuri; Fiscal Year: 2009
    ..association of the PI3 kinases ATM/ATR with damaged chromatin and subsequent activation of the checkpoint kinases (Chk1 and Chk2) and p53, as well as other regulatory proteins that control the fate of a cell following DNA damage...
  47. DNA Damage Signaling in Human Cancer Cells
    Fred Bunz; Fiscal Year: 2007
    ..unreadable] Aim 2. Analysis of human CHK1 activation in DNA damage responses...
  48. Samir S El-Dahr; Fiscal Year: 2014
    ..activation, BdkrB2 is required to prevent the phosphorylation of p53 on Ser23 by Checkpoint kinase 1 (Chk1). p-p53Ser23 is the central mediator of renal dysgenesis in BdkrB2-/- mutant mice...
  49. Inhibition of skin cancer by caffeine: Effects on late stages of carcinogenesis
    YAOPING LU; Fiscal Year: 2012
    ..Our leading hypothesis is that caffeine induces apoptosis by inhibition of the ATR/Chk1-dependent G2/M cell cycle checkpoint leading to premature mitosis and cell death...
  50. Bruce J Shenker; Fiscal Year: 2015
    ..three synergistic downstream events: FOXO3 activation leading to expression of cyclin G1 and/or G2, activation of Chk1 and the G2 checkpoint and accumulation of PI-3,4-P2 and localization of the adaptor protein, TAPP1...
  51. MICHAEL ALTERMAN LAMPSON; Fiscal Year: 2016
    ..There is evidence for interactions between Aurora B, BubR1, Plk1, and Chk1. By combining quantitative measurements of phosphorylation dynamics in living cells with kinase inhibition, using ..
  52. Jonathan Maybaum; Fiscal Year: 2015
    ..Drugs that target the checkpoint protein Chk1 (such as AZD7762, currently in Phase-I clinical trials) are of particular interest in the context of pancreatic ..
  53. ALAN R EASTMAN; Fiscal Year: 2016
    ..b>Chk1 has been identified as a critical kinase for cell cycle arrest and many inhibitors are currently in preclinical and ..
  54. Targeting Cell Cycle Checkpoints in Cancer Therapeutics
    Archie Tse; Fiscal Year: 2009
    ..Our initial focus was on 7-hydroxystaurosporine (UCN-01), an inhibitor of the critical checkpoint kinase, Chk1. UCN-01 potentiates cytotoxicity of the topoisomerase I poison, SN-38, by abrogating the S and G2/M checkpoints...
  55. microRNA function in human embryonic stem cells division
    Junlin Qi; Fiscal Year: 2009
    ..Another predicted target for miR-195, also a negative cell cycle regulator, is CHK1. We will test if CHK1 is a real miR-195 target and whether CHK1 is utilized to control hESC cell cycle...
  56. Luo Lu; Fiscal Year: 2016
    ..determine whether hypoxia-induced Plk3 can directly activate p53, AP-1 and H2AX, and how hypoxia-induced ATM/ATR/Chk1/2 activation leads to Plk3 activation in CE cells...
  57. Richard J Bram; Fiscal Year: 2015
    ..knockdown of CypB enhanced ER stress, and led to elevated reactive oxygen species (ROS) and decreased levels of Chk1 and mutant p53, as well as decreased activation of Stat3, all of which have been implicated in regulation of cancer ..
  58. Richard J Bram; Fiscal Year: 2015
    ..biochemical changes, including elevated reactive oxygen species (ROS) and decreased expression of mutant p53, and Chk1, as well as decreased activation of Stat3, all of which have been implicated in regulation of GBM proliferation...
  59. Inhibitory effects of caffeine, exercise and lipectomy on UVB-induced skin cancer
    YAOPING LU; Fiscal Year: 2012
    ..in combination with orally administered caffeine for 2 weeks on UVB-induced modulation of the p53-independent, ATR/Chk1/cyclin B1-mediated pathway that leads to lethal mitosis (apoptosis) in the epidermis of SKH-1 mice. 2...
  60. Samuel Sidi; Fiscal Year: 2016
    ..This proposal focuses on an emerging apoptotic pathway, designated 'Chk1-suppressed'(CS) apoptosis, whose activation by Chk1 inhibitors restores radiosensitivity in p53-deficient ..
  61. Building a Systems-Level View of Cell Cycle Checkpoints
    Jill Sible; Fiscal Year: 2009
    ..view of how unreplicated DNA affects the cell cycle engine is in hand, the model will be extended to include the Chk1 kinase signaling pathway, a key potential target for cancer chemotherapeutics...
  62. Cylcin G1/S Expression and Radiation Sensitivity
    Francisco Pardo; Fiscal Year: 2004
    ..is, at least in part, influenced by expression of the S-phase DNA repair regulatory pathways involving Chk1, Mre-11, and Nbs-1...
  63. Hua Lu; Fiscal Year: 2016
    ..I hypothesize that hypoxia may induce the association of 14-3-3? with MDMX that is phosphorylated by the ATR-ChK1 cascade, consequently suppressing MDMX activity and leading to p53 activation...
  64. Histidine Kinase 2-Component Protein of Candida Albicans
    Richard Calderone; Fiscal Year: 2009
    ..albicans, Ssklp, regulate expression of a CHK1-promoter-lacZ reporter suggesting that the HOG1 MAP kinase pathway may interact with Chklp...