CHK2

Summary

Gene Symbol: CHK2
Description: checkpoint kinase 2
Alias: CDS1, CHK2, HuCds1, LFS2, PP1425, RAD53, hCds1, CHK2 checkpoint homolog, cds1 homolog, checkpoint-like protein CHK2
Species: human

Top Publications

  1. ncbi CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?
    Laurent Antoni
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Nat Rev Cancer 7:925-36. 2007
  2. ncbi DNA damage-induced activation of p53 by the checkpoint kinase Chk2
    A Hirao
    The Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario, M5G 2C1, Canada
    Science 287:1824-7. 2000
  3. ncbi Linkage of ATM to cell cycle regulation by the Chk2 protein kinase
    S Matsuoka
    Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Science 282:1893-7. 1998
  4. 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
  5. ncbi ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex
    Ji Hoon Lee
    Department of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, 1 University Station, A4800, Austin, TX 78712, USA
    Science 308:551-4. 2005
  6. pmc A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint
    Marcel A T M van Vugt
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    PLoS Biol 8:e1000287. 2010
  7. doi A novel Chk1/2-Lats2-14-3-3 signaling pathway regulates P-body formation in response to UV damage
    Nobuhiro Okada
    Department of Molecular Genetics, Research Institute for MicroFbial Diseases, Osaka University, 3 1 Yamadaoka, Suita City, Osaka 565 0871, Japan
    J Cell Sci 124:57-67. 2011
  8. doi A protein phosphatase feedback mechanism regulates the basal phosphorylation of Chk2 kinase in the absence of DNA damage
    Luigi Carlessi
    Dept of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
    Biochim Biophys Acta 1803:1213-23. 2010
  9. ncbi The EBNA-3 gene family proteins disrupt the G2/M checkpoint
    Kenia G Krauer
    Queensland Institute of Medical Research and Joint Oncology Program, University of Queensland, Brisbane, Australia
    Oncogene 23:1342-53. 2004
  10. ncbi The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe
    Maria Castedo
    CNRS UMR 8125, Institut Gustave Roussy, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Oncogene 23:4353-61. 2004

Research Grants

  1. GENETIC AND MOLECULAR ANALYSIS OF YEAST DNA REPLICATION
    Robert A Sclafani; Fiscal Year: 2012
  2. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
  3. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
  4. ENZYMOLOGY OF REPLICATION OF YEAST CHROMOSOMAL DNA
    Peter M Burgers; Fiscal Year: 2012
  5. PROBES FOR CYTOMETRY
    Zbigniew Darzynkiewicz; Fiscal Year: 2013
  6. A Novel Pathway Involving ATM, PP1 and I-2
    Sankar Mitra; Fiscal Year: 2012
  7. Protein Kinase Signaling and Cell Cycle Control
    Michael B Yaffe; Fiscal Year: 2013
  8. ATF2 in DNA damage response.
    ZE apos EV A RONAI; Fiscal Year: 2010
  9. SOMATIC CELL CYCLE REGULATION BY PHOSPHORYLATION
    TONY R HUNTER; Fiscal Year: 2013
  10. Regulatory networks in DNA damage checkpoint response
    KATSONURI SUGIMOTO; Fiscal Year: 2013

Detail Information

Publications252 found, 100 shown here

  1. ncbi CHK2 kinase: cancer susceptibility and cancer therapy - two sides of the same coin?
    Laurent Antoni
    Cancer Research UK Centre for Cancer Therapeutics, Institute of Cancer Research, Haddow Laboratories, 15 Cotswold Road, Sutton, Surrey, SM2 5NG, UK
    Nat Rev Cancer 7:925-36. 2007
    In the past decade, CHK2 has emerged as an important multifunctional player in the DNA-damage response signalling pathway...
  2. ncbi DNA damage-induced activation of p53 by the checkpoint kinase Chk2
    A Hirao
    The Amgen Institute, Ontario Cancer Institute, and Departments of Medical Biophysics and Immunology, University of Toronto, 620 University Avenue, Suite 706, Toronto, Ontario, M5G 2C1, Canada
    Science 287:1824-7. 2000
    b>Chk2 is a protein kinase that is activated in response to DNA damage and may regulate cell cycle arrest. We generated Chk2-deficient mouse cells by gene targeting...
  3. ncbi Linkage of ATM to cell cycle regulation by the Chk2 protein kinase
    S Matsuoka
    Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Science 282:1893-7. 1998
    ..We identified Chk2, the mammalian homolog of the Saccharomyces cerevisiae Rad53 and Schizosaccharomyces pombe Cds1 protein kinases required for the DNA damage and replication checkpoints...
  4. 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
    ..The human homolog of the second S. pombe checkpoint kinase, Cds1 (CHK2/hCds1), phosphorylates tetrameric p53 but not monomeric p53 in vitro at sites similar to those phosphorylated by hCHK1 ..
  5. ncbi ATM activation by DNA double-strand breaks through the Mre11-Rad50-Nbs1 complex
    Ji Hoon Lee
    Department of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, 1 University Station, A4800, Austin, TX 78712, USA
    Science 308:551-4. 2005
    ..in vitro with DNA in the presence of MRN, leading to phosphorylation of the downstream cellular targets p53 and Chk2. ATM autophosphorylation was not required for monomerization of ATM by MRN...
  6. pmc A mitotic phosphorylation feedback network connects Cdk1, Plk1, 53BP1, and Chk2 to inactivate the G(2)/M DNA damage checkpoint
    Marcel A T M van Vugt
    David H Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
    PLoS Biol 8:e1000287. 2010
    ..Importantly, we show that Plk1 also phosphorylates the 53BP1-binding checkpoint kinase Chk2 to inactivate its FHA domain and inhibit its kinase activity in mammalian cells...
  7. doi A novel Chk1/2-Lats2-14-3-3 signaling pathway regulates P-body formation in response to UV damage
    Nobuhiro Okada
    Department of Molecular Genetics, Research Institute for MicroFbial Diseases, Osaka University, 3 1 Yamadaoka, Suita City, Osaka 565 0871, Japan
    J Cell Sci 124:57-67. 2011
    ..UV) radiation, the Lats2 tumor suppressor protein is phosphorylated predominantly by Chk1 and weakly by Chk2 at S408 in vivo, and that this process occurs at all stages of the cell cycle and leads to phosphorylation of 14-3-..
  8. doi A protein phosphatase feedback mechanism regulates the basal phosphorylation of Chk2 kinase in the absence of DNA damage
    Luigi Carlessi
    Dept of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy
    Biochim Biophys Acta 1803:1213-23. 2010
    The checkpoint kinase Chk2 is an effector component of the ATM-dependent DNA damage response (DDR) pathway. The activation of Chk2 by genotoxic stress involves its phosphorylation on T68 by ATM and additional auto/transphosphorylations...
  9. ncbi The EBNA-3 gene family proteins disrupt the G2/M checkpoint
    Kenia G Krauer
    Queensland Institute of Medical Research and Joint Oncology Program, University of Queensland, Brisbane, Australia
    Oncogene 23:1342-53. 2004
    ..The function of EBNA-3, -4 and -6 proteins appears to be more complex than anticipated and these data suggest a role for these proteins in disrupting the host cell cycle machinery...
  10. ncbi The cell cycle checkpoint kinase Chk2 is a negative regulator of mitotic catastrophe
    Maria Castedo
    CNRS UMR 8125, Institut Gustave Roussy, 39 rue Camille Desmoulins, F 94805 Villejuif, France
    Oncogene 23:4353-61. 2004
    ..that the down regulation of Cdk1/cyclin B is secondary to the activation of the DNA structure checkpoint kinase Chk2. Thus, syncytia generated by the fusion of asynchronous HeLa cells contain elevated levels of active Chk2 but not ..
  11. pmc Family history, genetic testing, and clinical risk prediction: pooled analysis of CHEK2 1100delC in 1,828 bilateral breast cancers and 7,030 controls
    Olivia Fletcher
    Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London United Kingdom
    Cancer Epidemiol Biomarkers Prev 18:230-4. 2009
    ..Before such predictions are accepted by clinical geneticists, however, further population-based evidence is needed on the effect of CHEK2 1100delC and other moderate penetrance alleles in women with a family history of breast cancer...
  12. doi The cell cycle checkpoint kinase CHK2 mediates DNA damage-induced stabilization of TTK/hMps1
    Y H Yeh
    Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
    Oncogene 28:1366-78. 2009
    ..We have demonstrated previously that, upon DNA damage, TTK/hMps1 activates the checkpoint kinase CHK2 by phosphorylating CHK2 at Thr68...
  13. pmc Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro
    S Matsuoka
    Howard Hughes Medical Institute, Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA
    Proc Natl Acad Sci U S A 97:10389-94. 2000
    The protein kinase Chk2, the mammalian homolog of the budding yeast Rad53 and fission yeast Cds1 checkpoint kinases, is phosphorylated and activated in response to DNA damage by ionizing radiation (IR), UV irradiation, and replication ..
  14. ncbi Activation of ATM and Chk2 kinases in relation to the amount of DNA strand breaks
    Giacomo Buscemi
    Department of Experimental Oncology, Istituto Nazionale Tumori, Via G Venezian 1, 20133 Milan, Italy
    Oncogene 23:7691-700. 2004
    ..Here, we determined the kinetics of activation of the checkpoint kinases ATM and Chk2 (the latter substrate of ATM) in relation to the initial yield of genomic DNA single-strand (SSBs) and double-..
  15. ncbi Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2
    Jiejin Li
    Division of Protein Structure, National Institute for Medical Research, The Ridgeway, Mill Hill, London, United Kingdom
    Mol Cell 9:1045-54. 2002
    The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage...
  16. ncbi PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2
    Shutong Yang
    Laboratory of Biochemical Genetics, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
    Nat Cell Biol 4:865-70. 2002
    ..The DNA damage checkpoint kinase hCds1/Chk2 is necessary for p53-dependent apoptosis after gamma irradiation...
  17. ncbi Caffeine abolishes the mammalian G(2)/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity
    B B Zhou
    Department of Oncology Research, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406, USA
    J Biol Chem 275:10342-8. 2000
    ..inhibits such a change and markedly reduces radiation-induced ataxia-telangiectasia-mutated (ATM)-dependent Chk2/Cds1 activation and phosphorylation...
  18. doi Structure and activation mechanism of the CHK2 DNA damage checkpoint kinase
    Zhenjian Cai
    Structural Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA
    Mol Cell 35:818-29. 2009
    The CHK2 protein kinase is an important transducer of DNA damage checkpoint signals, and its mutation contributes to hereditary and sporadic cancer...
  19. pmc Naphthalimides induce G(2) arrest through the ATM-activated Chk2-executed pathway in HCT116 cells
    Hong Zhu
    Division of Anti tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, PR China
    Neoplasia 11:1226-34. 2009
    ..Furthermore, depletion of Chk2, but not Chk1 with their corresponding siRNA, statistically significantly reversed the R16- and amonafide-triggered ..
  20. pmc CHEK2 contribution to hereditary breast cancer in non-BRCA families
    Alexis Desrichard
    Laboratoire Diagnostic Génétique et Moléculaire, Centre Jean Perrin, 58 rue Montalembert, F 63011 Clermont Ferrand, France
    Breast Cancer Res 13:R119. 2011
    ..Previous studies have demonstrated an association between CHEK2 founder mutations and non-BRCA HBC. However, very few data on the entire coding sequence of this gene are available...
  21. pmc Roles of Kruppel-associated Box (KRAB)-associated Co-repressor KAP1 Ser-473 Phosphorylation in DNA Damage Response
    Chen Hu
    Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and College of Life Science and
    J Biol Chem 287:18937-52. 2012
    ..Ataxia telangiectasia mutated (ATM)-Chk2 and ATM- and Rad3-related (ATR)-Chk1 are two primary kinase signaling cascades activated in response to DNA damage...
  22. pmc Role of the ATM-checkpoint kinase 2 pathway in CDT-mediated apoptosis of gingival epithelial cells
    Mounia Alaoui-El-Azher
    Department of Oral Biology and Center for Molecular Microbiology, College of Dentistry, University of Florida, Gainesville, Florida, United States of America
    PLoS ONE 5:e11714. 2010
    ..inhibition and siRNA-silencing of the ATM downstream effector, the protein kinase checkpoint kinase 2 (Chk2), significantly impacted CDT-mediated apoptosis...
  23. pmc CHEK2 is a multiorgan cancer susceptibility gene
    C Cybulski
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
    Am J Hum Genet 75:1131-5. 2004
    ..0; P=.001), kidney cancer (OR 2.1; P=.0006), prostate cancer (OR 1.7; P=.002), and thyroid cancer (OR 1.9; P=.04). The range of cancers associated with mutations of the CHEK2 gene may be much greater than previously thought...
  24. pmc Phosphorylation of HuR by Chk2 regulates SIRT1 expression
    Kotb Abdelmohsen
    Laboratory of Cellular and Molecular Biology, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Mol Cell 25:543-57. 2007
    ..The cell cycle checkpoint kinase Chk2 was activated by H(2)O(2), interacted with HuR, and was predicted to phosphorylate HuR at residues S88, S100, and ..
  25. ncbi REGgamma/PA28gamma proteasome activator interacts with PML and Chk2 and affects PML nuclear bodies number
    Laura Zannini
    Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale Tumori, Milano 20133, Italy
    Cell Cycle 8:2399-407. 2009
    ..We additionally found that REGgamma interacts with the DNA damage checkpoint kinase Chk2, whose presence is necessary for the increase of PML-NBs induced by REGgamma deficiency, and that REGgamma ..
  26. pmc The CHEK2 1100delC mutation identifies families with a hereditary breast and colorectal cancer phenotype
    Hanne Meijers-Heijboer
    Department of Clinical Genetics, Erasmus MC, Rotterdam, The Netherlands
    Am J Hum Genet 72:1308-14. 2003
    ..The unequivocal definition of the HBCC phenotype opens new avenues to search for this putative HBCC-susceptibility gene...
  27. ncbi HIV-1 Vpr induces ATM-dependent cellular signal with enhanced homologous recombination
    C Nakai-Murakami
    Department of Intractable Diseases, International Medical Center of Japan, Shinjuku ku, Tokyo, Japan
    Oncogene 26:477-86. 2007
    ..study, we present evidence that Vpr also activates ATM, and induces expression of gamma-H2AX and phosphorylation of Chk2. Strikingly, Vpr was found to stimulate the focus formation of Rad51 and BRCA1, which are involved in repair of DNA ..
  28. doi The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage
    E M Bahassi
    Department of Cell and Cancer Biology, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
    Oncogene 27:3977-85. 2008
    ..The checkpoint kinases Chk1 and Chk2 phosphorylate the carboxy-terminal domain of hBRCA2, a protein involved in recombination-mediated DNA repair (HRR) ..
  29. pmc Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes
    Yongjun Tan
    Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL 60607, USA
    Mol Cell Biol 27:1007-16. 2007
    ..Furthermore, FoxM1 protein is phosphorylated by checkpoint kinase 2 (Chk2) in response to DNA damage...
  30. ncbi Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations
    Hanne Meijers-Heijboer
    Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands
    Nat Genet 31:55-9. 2002
    ..To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint kinase that is implicated in DNA repair processes involving BRCA1 and p53 (..
  31. ncbi Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain
    Joon Young Ahn
    Department of Hematology Oncology, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    J Biol Chem 277:19389-95. 2002
    Phosphorylation of Thr-68 by the ataxia telangiectasia-mutated is necessary for efficient activation of Chk2 when cells are exposed to ionizing radiation...
  32. ncbi Karyopherin-alpha2 protein interacts with Chk2 and contributes to its nuclear import
    Laura Zannini
    Department of Experimental Oncology, Istituto Nazionale Tumori, Via G Venezian 1, 20133 Milan, Italy
    J Biol Chem 278:42346-51. 2003
    b>Chk2 is a nuclear protein kinase involved in the DNA damage-induced ataxia telangiectasia mutated-dependent checkpoint arrest at multiple cell cycle phases...
  33. pmc Chk2/hCds1 functions as a DNA damage checkpoint in G(1) by stabilizing p53
    N H Chehab
    Department of Molecular Genetics, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA
    Genes Dev 14:278-88. 2000
    Chk2/hcds1, the human homolog of the Saccharomyces cerevisiae RAD53/SPK1 and Schizosaccharomyces pombe cds1 DNA damage checkpoint genes, encodes a protein kinase that is post-translationally modified after DNA damage...
  34. doi Estrogen receptor status in CHEK2-positive breast cancers: implications for chemoprevention
    C Cybulski
    Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
    Clin Genet 75:72-8. 2009
    ..01). Women with a CHEK2 mutation face a fourfold increase in the risk of ER-positive breast cancer and might be candidates for tamoxifen chemoprevention...
  35. doi Chk2 oligomerization studied by phosphopeptide ligation: implications for regulation and phosphodependent interactions
    Jiejin Li
    Division of Molecular Structure, MRC National Institute for Medical Research, The Ridgeway, London NW7 1AA, United Kingdom
    J Biol Chem 283:36019-30. 2008
    Chk2/CHEK2/hCds1 is a modular serine-threonine kinase involved in transducing DNA damage signals. Phosphorylation by ataxia telangiectasia-mutated kinase (ATM) promotes Chk2 self-association, autophosphorylation, and activation...
  36. doi Short 42 degrees C heat shock induces phosphorylation and degradation of Cdc25A which depends on p38MAPK, Chk2 and 14.3.3
    Sibylle Madlener
    Institute of Clinical Pathology, Medical University of Vienna, Austria
    Hum Mol Genet 18:1990-2000. 2009
    ..Cdc25A degradation depended on Ser75-Cdc25A phosphorylation caused by p38MAPK and Chk2, which phosphorylated Ser177-Cdc25A that is specific for 14.3.3 binding...
  37. ncbi Stability of checkpoint kinase 2 is regulated via phosphorylation at serine 456
    Elizabeth M Kass
    Department of Biological Sciences, Columbia University, New York, New York, 10027 and Cell Signaling Technology, Inc, Danvers, Massachusetts 01923
    J Biol Chem 282:30311-21. 2007
    Checkpoint kinase 2 (Chk2), a DNA damage-activated protein kinase, is phosphorylated at Thr-68 by ataxia telangiectasia mutated leading to its activation by phosphorylation at several additional sites...
  38. ncbi Polo-like kinase 1 and Chk2 interact and co-localize to centrosomes and the midbody
    Lyuben Tsvetkov
    Department of Pathology, School of Medicine, Yale University, New Haven, Connecticut 06511, USA
    J Biol Chem 278:8468-75. 2003
    b>Chk2 is a protein kinase intermediary in DNA damage checkpoint pathways. DNA damage induces phosphorylation of Chk2 at multiple sites concomitant with activation...
  39. ncbi Is CHEK2 a cause of the Li-Fraumeni syndrome?
    D G Evans
    J Med Genet 45:63-4. 2008
  40. doi CHEK2*1100delC homozygosity is associated with a high breast cancer risk in women
    Muriel A Adank
    Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands
    J Med Genet 48:860-3. 2011
    ..This study investigated the occurrence of homozygosity for the CHEK2*1100delC allele among familial breast cancer cases and the associated breast cancer risk...
  41. pmc Taking the time to make important decisions: the checkpoint effector kinases Chk1 and Chk2 and the DNA damage response
    Travis H Stracker
    Molecular Biology, Sloan Kettering Institute, New York, NY, USA
    DNA Repair (Amst) 8:1047-54. 2009
    ..Key components of the DDR in mammalian cells are the checkpoint effector kinases Chk1 and Chk2 (referred to henceforth as the effector kinases; orthologous to spChk1 and spCds1 in the fission yeast S...
  42. pmc X-ray structures of checkpoint kinase 2 in complex with inhibitors that target its gatekeeper-dependent hydrophobic pocket
    George T Lountos
    Basic Science Program, SAIC Frederick, Frederick, MD 21702 1201, USA
    FEBS Lett 585:3245-9. 2011
    The serine/threonine checkpoint kinase 2 (Chk2) is an attractive molecular target for the development of small molecule inhibitors to treat cancer...
  43. doi The risk of gastric cancer in carriers of CHEK2 mutations
    Urszula Teodorczyk
    Department of Genetics and Pathology, International Hereditary Cancer Centre, Pomeranian Medical University, Szczecin, Poland
    Fam Cancer 12:473-8. 2013
    ..4, p = 0.05). Truncating mutations of CHEK2 were associated with higher risk (OR = 2.1, p = 0.02) than the missense mutation I157T (OR = 1.4, p = 0.04). CHEK2 mutations predispose to gastric cancer, in particular to young-onset cases...
  44. ncbi Inducible degradation of checkpoint kinase 2 links to cisplatin-induced resistance in ovarian cancer cells
    Peilin Zhang
    Department of Pathology, West Virginia University, Morgantown, WV 26506, USA
    Biochem Biophys Res Commun 328:567-72. 2005
    Checkpoint kinase 2 (Chk2) is one of the critical kinases governing the cell cycle checkpoint, DNA damage repair, and cell apoptosis in response to DNA damaging signals...
  45. doi The shelterin protein TRF2 inhibits Chk2 activity at telomeres in the absence of DNA damage
    Giacomo Buscemi
    Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133, Italy
    Curr Biol 19:874-9. 2009
    ..Here we show that in human undamaged cells, a fraction of the kinase Chk2, a downstream target of ATM and mediator of checkpoint responses and senescence [4, 5], physically interacts with ..
  46. pmc The DNA damage sensors ataxia-telangiectasia mutated kinase and checkpoint kinase 2 are required for hepatitis C virus RNA replication
    Yasuo Ariumi
    Department of Molecular Biology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2 5 1, Shikata cho, Okayama 700 8558, Japan
    J Virol 82:9639-46. 2008
    ..kinase (ATM), ATM- and Rad3-related kinase (ATR), poly(ADP-ribose) polymerase 1 (PARP-1), and checkpoint kinase 2 (Chk2), play central roles in the response to genotoxic stress, we hypothesized that these sensors might affect HCV ..
  47. pmc Phosphorylation at threonine 288 by cell cycle checkpoint kinase 2 (CHK2) controls human monopolar spindle 1 (Mps1) kinetochore localization
    Chun Wei Yeh
    From the Institute of Biomedical Sciences, Academia Sinica, 128 Sec 2, Academia Road, Taipei 115, Taiwan
    J Biol Chem 289:15319-27. 2014
    ..Here, we demonstrate that phosphorylation at Thr-288 by the cell cycle checkpoint kinase CHK2 is involved in this process...
  48. pmc Chk2 activation dependence on Nbs1 after DNA damage
    G Buscemi
    Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milan, Italy
    Mol Cell Biol 21:5214-22. 2001
    The checkpoint kinase Chk2 has a key role in delaying cell cycle progression in response to DNA damage...
  49. doi The effect of CHEK2 variant I157T on cancer susceptibility: evidence from a meta-analysis
    Fei fei Han
    Beijing Chao Yang Hospital, Capital Medical University, Beijing, China
    DNA Cell Biol 32:329-35. 2013
    ....
  50. pmc Mutation analysis of the CHK2 gene in breast carcinoma and other cancers
    Sigurdur Ingvarsson
    Institute for Experimental Pathology, University of Iceland, Reykjavik, Iceland
    Breast Cancer Res 4:R4. 2002
    Mutations in the CHK2 gene at chromosome 22q12.1 have been reported in families with Li-Fraumeni syndrome. Chk2 is an effector kinase that is activated in response to DNA damage and is involved in cell-cycle pathways and p53 pathways.
  51. doi A simple method of investigating mutations in CHEK2 by DHPLC: a study of the German populations of Saxony, Saxony-Anhalt, and Thuringia
    Ulrike Scharrer
    Institute of Human Genetics, University of Leipzig, Germany
    Cancer Genet Cytogenet 199:48-52. 2010
    ..It can be easily integrated into diagnostic testing...
  52. doi Effect of CHEK2 missense variant I157T on the risk of breast cancer in carriers of other CHEK2 or BRCA1 mutations
    C Cybulski
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul Połabska 4, Szczecin, Poland
    J Med Genet 46:132-5. 2009
    ..However, it is of interest to estimate the breast cancer risks associated with carrying two mutations because this information may be informative for genetic counsellors and may provide clues to the carcinogenic process...
  53. pmc Risk for contralateral breast cancer among carriers of the CHEK2*1100delC mutation in the WECARE Study
    L Mellemkjaer
    Institute of Cancer Epidemiology, Danish Cancer Society, Strandboulevarden 49, DK 2100 Copenhagen, Denmark
    Br J Cancer 98:728-33. 2008
    ..However, the sampling variability was such that modest increases in risk could not be excluded. Nonetheless, because this is a rare mutation, it is unlikely to explain a major fraction of CBC in the population...
  54. doi The CHEK2 1100delC mutation is not present in Korean patients with breast cancer cases tested for BRCA1 and BRCA2 mutation
    Doo Ho Choi
    Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangnam Gu, Seoul, South Korea
    Breast Cancer Res Treat 112:569-73. 2008
    ..However, our results suggest that this mutation is absent or may be very infrequent in Korean patients with breast cancer who have high risk of BRCA1 and BRCA2 mutation, making its screening irrelevant from the practical point view...
  55. ncbi Pathology of breast cancer in women with constitutional CHEK2 mutations
    Tomasz Huzarski
    Pomeranian Medical University, Szczecin, Poland
    Breast Cancer Res Treat 90:187-9. 2005
    ..6; p > 0.0001). This is the first report to demonstrate that different mutations of the same gene may be associated with specific histologic subtypes of cancer...
  56. 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
    ..These results indicate that serine-216 phosphorylation and 14-3-3 binding negatively regulate Cdc25C and identify Cdc25C as a potential target of checkpoint control in human cells...
  57. ncbi Direct activation of the ATM protein kinase by the Mre11/Rad50/Nbs1 complex
    Ji Hoon Lee
    Department of Molecular Genetics and Microbiology, Institute of Cellular and Molecular Biology, University of Texas at Austin, 1 University Station, A4800, Austin, TX 78712, USA
    Science 304:93-6. 2004
    ..We demonstrate that MRN stimulates the kinase activity of ATM in vitro toward its substrates p53, Chk2, and histone H2AX...
  58. pmc Mutations in CHEK2 associated with prostate cancer risk
    Xiangyang Dong
    Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic Mayo Medical School, Rochester, MN 55905, USA
    Am J Hum Genet 72:270-80. 2003
    ..Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer...
  59. ncbi The Wip1 phosphatase (PPM1D) antagonizes activation of the Chk2 tumour suppressor kinase
    M Oliva-Trastoy
    Service de Biochimie et de Génétique Moléculaire, CEA Saclay, Gif sur Yvette, France
    Oncogene 26:1449-58. 2007
    ..In response to DNA damage, ataxia telangiectasia mutated (ATM) phosphorylates the Chk2 tumour suppressor kinase at threonine 68 (Thr68), allowing Chk2 kinase dimerization and activation by ..
  60. pmc Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange
    Antony W Oliver
    Section of Structural Biology, Cancer Research UK DNA Repair Enzymes Group, The Institute of Cancer Research, Chelsea, London, UK
    EMBO J 25:3179-90. 2006
    The protein kinase Chk2 (checkpoint kinase 2) is a major effector of the replication checkpoint. Chk2 activation is initiated by phosphorylation of Thr68, in the serine-glutamine/threonine-glutamine cluster domain (SCD), by ATM...
  61. ncbi Chk2 activates E2F-1 in response to DNA damage
    Craig Stevens
    Division of Biochemistry and Molecular Biology, Davidson Building, University of Glasgow, Glasgow, G12 8QQ, UK
    Nat Cell Biol 5:401-9. 2003
    ..We report that checkpoint kinase 2 (Chk2) regulates E2F-1 activity in response to the DNA-damaging agent etoposide...
  62. doi Constitutional CHEK2 mutations are associated with a decreased risk of lung and laryngeal cancers
    Cezary Cybulski
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, ul Połabska 4, 70 115 Szczecin, Poland
    Carcinogenesis 29:762-5. 2008
    ..g. p53 mutations) and have a high level of genotoxic DNA damage induced by tobacco smoke. We speculate that lung cancer cells with impaired CHEK2 function undergo increased rates of cell death...
  63. ncbi hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response
    J S Lee
    Laboratory of Molecular Hematology, NHLBI, NIH, Bethesda, Maryland 20892, USA
    Nature 404:201-4. 2000
    ..Here we report that the human Cds1 kinase (hCds1/Chk2) regulates BRCA1 function after DNA damage by phosphorylating serine 988 of BRCA1...
  64. pmc Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts
    Daphne W Bell
    Massachusetts General Hospital Cancer Center, Charlestown, MA, USA
    Int J Cancer 121:2661-7. 2007
    ....
  65. pmc A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer
    Pia Vahteristo
    Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Haartmaninkatu 8, FIN 00029 HUS, Helsinki, Finland
    Am J Hum Genet 71:432-8. 2002
    CHEK2 (previously known as "CHK2") is a cell-cycle-checkpoint kinase that phosphorylates p53 and BRCA1 in response to DNA damage...
  66. ncbi The CHEK2 gene and inherited breast cancer susceptibility
    H Nevanlinna
    Department of Obstetrics and Gynecology, Helsinki University Central Hospital, Helsinki, Finland
    Oncogene 25:5912-9. 2006
    Checkpoint kinase 2 (CHEK2, Chk2) emerges as an important signal transducer of cellular responses to DNA damage and a candidate tumor suppressor whose defects contribute to molecular pathogenesis of diverse types of human malignancies, ..
  67. ncbi Regulation of the Chk2 protein kinase by oligomerization-mediated cis- and trans-phosphorylation
    Julie K Schwarz
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA
    Mol Cancer Res 1:598-609. 2003
    b>Chk2 is a serine/threonine protein kinase found mutated in certain hereditary and sporadic cancers. Ionizing radiation (IR) activates the kinase activity of Chk2 in a phosphorylation-dependent manner...
  68. pmc Frequency of CHEK2 mutations in a population based, case-control study of breast cancer in young women
    Danielle M Friedrichsen
    Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA
    Breast Cancer Res 6:R629-35. 2004
    ..However, the 1100delC mutation has only been investigated in a few population-based studies and none from North America...
  69. ncbi The association of sequence variants in DNA repair and cell cycle genes with cancers of the upper aerodigestive tract
    Janet Hall
    International Agency for Research on Cancer, Lyon, France
    Carcinogenesis 28:665-71. 2007
    ..While some of these associations are consistent with previous studies, we cannot rule out the possibility of false-positive associations. The positive findings should be explored in another large-scale study on UADT cancers...
  70. pmc CHEK2 mutations affecting kinase activity together with mutations in TP53 indicate a functional pathway associated with resistance to epirubicin in primary breast cancer
    Ranjan Chrisanthar
    Section of Oncology, Institute of Medicine, University of Bergen, Bergen, Norway
    PLoS ONE 3:e3062. 2008
    ..critical mechanisms activating p53 in response to DNA damage in breast cancer; 3) Evaluate in vitro function of Chk2 and p14 proteins corresponding to identified mutations in the CHEK2 and p14((ARF)) genes; and 4) Explore potential ..
  71. doi The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells
    Ailine Stolz
    Philipps University Marburg, Institute for Molecular Biology and Tumour Research IMT, D 35037 Marburg, Germany
    Nat Cell Biol 12:492-9. 2010
    ..The Chk2 kinase and its downstream targets p53 and Brca1 are tumour suppressors that have been functionally linked to the ..
  72. ncbi Regulation of CHK2 by DNA-dependent protein kinase
    Jia Li
    Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
    J Biol Chem 280:12041-50. 2005
    b>Chk2 is a critical mediator of diverse cellular responses to DNA damage. Activation of Chk2 by DNA damage requires phosphorylation at sites including Thr68...
  73. ncbi CHEK2-positive breast cancers in young Polish women
    Cezary Cybulski
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
    Clin Cancer Res 12:4832-5. 2006
    ..To investigate the contribution of CHEK2 mutations to early-onset breast cancer in Poland and to establish the characteristic features of these cancers...
  74. ncbi The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis
    J Falck
    Institute of Cancer Bioloyg, Danish Cancer Society, Copenhagen, Denmark
    Nature 410:842-7. 2001
    ..Here we report a functional link between ATM, the checkpoint signalling kinase Chk2/Cds1 (Chk2) and Cdc25A, and implicate this mechanism in controlling the S-phase checkpoint...
  75. doi Evaluation of variants in the CHEK2, BRIP1 and PALB2 genes in an Irish breast cancer cohort
    N M McInerney
    Department of Surgery, Clinical Science Institute, University College Hospital, Galway, Ireland
    Breast Cancer Res Treat 121:203-10. 2010
    ..We found no evidence to suggest that PALB2 mutation is an important breast cancer predisposition gene in this population...
  76. ncbi The Chk2 tumor suppressor is not required for p53 responses in human cancer cells
    Prasad V Jallepalli
    The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University, Baltimore, Maryland 21231, USA
    J Biol Chem 278:20475-9. 2003
    Ionizing radiation damages chromosomal DNA and activates p53-dependent transcription in mammalian cells. The Chk2 protein kinase has been hypothesized to be the primary mediator of this response...
  77. pmc Tumour characteristics and prognosis of breast cancer patients carrying the germline CHEK2*1100delC variant
    G H de Bock
    Department of Medical Decision Making, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands
    J Med Genet 41:731-5. 2004
    ..The germline CHEK2*1100delC variant has been associated with breast cancer in multiple case families where involvement of BRCA1 and BRCA2 has been excluded...
  78. ncbi Germline mutations in the CHEK2 kinase gene are associated with an increased risk of bladder cancer
    Elzbieta Złowocka
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
    Int J Cancer 122:583-6. 2008
    ..A CHEK2 mutation (all variants combined) was found in 10.6% of the cancer cases and in 5.9% of the controls (OR = 1.9; 95%CI 1.3-2.7; p = 0.0003). We conclude that CHEK2 mutations increase the risk of bladder cancer in the population...
  79. pmc Identification of women with an increased risk of developing radiation-induced breast cancer: a case only study
    Annegien Broeks
    Division of Experimental Therapy, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Breast Cancer Res 9:R26. 2007
    ..Radiation exposure at a young age is one of the strongest risk factors for breast cancer. Germline mutations in genes involved in the DNA-damage repair pathway (DDRP) may render women more susceptible to radiation-induced breast cancer...
  80. ncbi Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population
    Avraham Shaag
    Department of Medicine Medical Genetics and Genome Sciences, University of Washington, Seattle, WA 98195 7720, USA
    Hum Mol Genet 14:555-63. 2005
    ..To assay these alleles for loss of CHEK2 function, we tested their capacity to complement Rad53 deletion in Saccharomyces cerevisiae. CHEK2...
  81. ncbi CHEK2 1100delC is not a risk factor for male breast cancer population
    Kirsi Syrjakoski
    Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland
    Int J Cancer 108:475-6. 2004
    ..A 1100delC mutation in CHEK2 (previously known as CHK2), a cell-cycle checkpoint kinase, has been implicated in predisposition of Li-Fraumeni syndrome (LFS) and breast ..
  82. ncbi A robust method for detecting CHK2/RAD53 mutations in genomic DNA
    Nayanta Sodha
    Royal Marsden NHS Trust, Surrey, UK
    Hum Mutat 19:173-7. 2002
    While screening for germline CHK2 mutations in cancer cases by heteroduplex CSGE, we observed that additional PCR fragments were generated from the 3' end region of the gene that includes exons 11-14...
  83. ncbi Activated checkpoint kinase 2 provides a survival signal for tumor cells
    Jagadish C Ghosh
    Department of Cancer Biology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
    Cancer Res 66:11576-9. 2006
    ..This is independent of p53, and requires activated checkpoint kinase 2 (Chk2), a putative tumor suppressor...
  84. ncbi Breast cancer predisposing alleles in Poland
    B Gorski
    Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Polabska 4, Szczecin, Poland 70 115
    Breast Cancer Res Treat 92:19-24. 2005
    ..1) than for the missense mutation I157T (OR=1.4). This study suggests that cancer risks may be specific for particular alleles of a susceptibility gene and that these different risks should be taken into account by genetic counselors...
  85. pmc Linkage disequilibrium mapping of CHEK2: common variation and breast cancer risk
    Kristjana Einarsdóttir
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
    PLoS Med 3:e168. 2006
    ..In this study, we aimed to assess the importance of common CHEK2 variants on population risk for breast cancer by capturing the majority of diversity in the gene using haplotype tagging single nucleotide polymorphisms (tagSNPs)...
  86. pmc DNA damage-induced cell cycle regulation and function of novel Chk2 phosphoresidues
    Giacomo Buscemi
    Department of Experimental Oncology, Istituto Nazionale Tumori, 20133 Milano, Italy
    Mol Cell Biol 26:7832-45. 2006
    b>Chk2 kinase is activated by DNA damage to regulate cell cycle arrest, DNA repair, and apoptosis...
  87. ncbi CHK2-decreased protein expression and infrequent genetic alterations mainly occur in aggressive types of non-Hodgkin lymphomas
    Frederic Tort
    Laboratory of Pathology, Hospital Clinic, Institut d Investigacions Biomediques August Pi i Sunyer IDIBAPS, University of Barcelona, Spain
    Blood 100:4602-8. 2002
    The CHK2 gene codifies for a serine/threonine kinase that plays a central role in DNA damage response pathways...
  88. ncbi Uncommon CHEK2 mis-sense variant and reduced risk of tobacco-related cancers: case control study
    Paul Brennan
    International Agency for Research on Cancer IARC, Lyon, France
    Hum Mol Genet 16:1794-801. 2007
    ..g. by forcing nearby stem cells to divide before they have repaired their own DNA damage from tobacco smoke). If so, reducing the rate of apoptosis by reducing CHEK2 activity could be protective-although not smoking would be far more so...
  89. pmc CHEK2 I157T associates with familial and sporadic colorectal cancer
    O Kilpivaara
    J Med Genet 43:e34. 2006
    ..We investigated the CHEK2 I157T variant for colorectal cancer (CRC) predisposition in a large population based study including a significant number of familial CRC cases...
  90. pmc Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility
    Mieke Schutte
    Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands
    Am J Hum Genet 72:1023-8. 2003
    ..These results indicate that 1100delC may be the only CHEK2 allele that makes an appreciable contribution to breast cancer susceptibility...
  91. ncbi Colorectal cancer and the CHEK2 1100delC mutation
    Mirjam M de Jong
    Department of Gastroenterology, University of Groningen Medical Center, The Netherlands
    Genes Chromosomes Cancer 43:377-82. 2005
    ..Together, the results are consistent with a low-penetrance effect (OR 1.5-2.0) of the CHEK2 1100delC on CRC risk. Large case-control studies are required to clarify the exact role of the CHEK2 1100delC mutation in CRC...
  92. doi CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26,000 patient cases and 27,000 controls
    Maren Weischer
    Department of Clinical Biochemistry, Herlev University Hospital, Herlev Ringvej 75, Herlev, Denmark
    J Clin Oncol 26:542-8. 2008
    ..CHEK2*1100delC heterozygosity may be associated with an increased risk of breast cancer; however, it is unclear whether the evidence is sufficient to recommend genotyping in clinical practice...
  93. ncbi Aberrations of the Chk2 tumour suppressor in advanced urinary bladder cancer
    Jirina Bartkova
    Institute of Cancer Biology, Danish Cancer Society, Strandboulevarden 49, Copenhagen DK 2100, Denmark
    Oncogene 23:8545-51. 2004
    Checkpoint kinase 2 (Chk2) is a tumour suppressor and signal transducer in genome integrity checkpoints that coordinate cell-cycle progression with DNA repair or cell death in response to DNA damage...
  94. ncbi Low frequency of the CHEK2*1100delC mutation among breast cancer probands from three regions of Poland
    E Kwiatkowska
    The Maria Sklodowska Curie Cancer Center and Institute of Oncology, 02781 Warsaw, Poland
    Neoplasma 53:305-8. 2006
    ..Further studies are still needed to evaluate the contribution of this mutation to the development of bilateral breast tumors...
  95. ncbi Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase
    H Fujimoto
    1Department of Genome Sciences, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, 7 5 1, Kusunoki cho, Chuo Ku, Kobe 650 0017, Japan
    Cell Death Differ 13:1170-80. 2006
    The antioncogenic Chk2 kinase plays a crucial role in DNA damage-induced cell-cycle checkpoint regulation...
  96. ncbi MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways
    Zhenkun Lou
    Department of Oncology, Mayo Foundation, Rochester, Minnesota 55905, USA
    Nature 421:957-61. 2003
    ..MDC1 localizes to sites of DNA breaks and associates with CHK2 after DNA damage. This association is mediated by the MDC1 FHA domain and the phosphorylated Thr 68 of CHK2...
  97. ncbi CHEK2 variants predispose to benign, borderline and low-grade invasive ovarian tumors
    J Szymanska-Pasternak
    International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland
    Gynecol Oncol 102:429-31. 2006
    ..Two founder alleles (1100delC and IVS2 + 1G >A) result in a truncated CHEK2 protein and the other is a missense substitution, leading to the replacement of a threonine with an isoleucine (I157T)...
  98. pmc Analysis of CHK2 in vulval neoplasia
    A Reddy
    Ludwig Institute for Cancer Research, Imperial College Faculty of Medicine, St Mary s Campus, Norfolk Place, London W2 1PG, UK
    Br J Cancer 86:756-60. 2002
    Structure and expression of the Rad53 homologue CHK2 were studied in vulval neoplasia...
  99. ncbi Endogenous gamma-H2AX-ATM-Chk2 checkpoint activation in Bloom's syndrome helicase deficient cells is related to DNA replication arrested forks
    V Ashutosh Rao
    Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, U S Department of Health and Human Services, Bethesda, Maryland, USA
    Mol Cancer Res 5:713-24. 2007
    ..DNA double-strand break checkpoint response with prominent levels of phosphorylated histone H2AX (gamma-H2AX), Chk2 (p(T68)Chk2), and ATM (p(S1981)ATM) colocalizing in nuclear foci...
  100. ncbi Protein phosphatase 2A interacts with Chk2 and regulates phosphorylation at Thr-68 after cisplatin treatment of human ovarian cancer cells
    Xiaobing Liang
    Department of Biochemistry and Molecular Pharmacology, Mary Babb Randolph Cancer Center, Robert C Byrd Health Sciences Center, West Virginia University, Morgantown, WV 26506 9300, USA
    Int J Mol Med 17:703-8. 2006
    ..The checkpoint kinase, Chk2, has been implicated in both of these responses...
  101. ncbi Breast cancer survival and tumor characteristics in premenopausal women carrying the CHEK2*1100delC germline mutation
    Marjanka K Schmidt
    Department of Epidemiology, Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands
    J Clin Oncol 25:64-9. 2007
    ....

Research Grants63

  1. GENETIC AND MOLECULAR ANALYSIS OF YEAST DNA REPLICATION
    Robert A Sclafani; Fiscal Year: 2012
    ..of important cell cycle protein kinases, which include DDK (Cdc7-Dbf4), CDK (cyclin-dependent kinase) and the Rad53 checkpoint kinase. Three specific aims are proposed...
  2. DNA Damage Checkpoint and Cancer
    Toru Ouchi; Fiscal Year: 2012
    ..pathways are responsible for arresting the cell cycle in response to damaged DNA - the ATR-Chk1 pathway and the ATM-Chk2 pathway...
  3. Functional study of C53 protein as a novel regulator of checkpoint kinases
    Honglin Li; Fiscal Year: 2012
    ..activating a network of molecules including protein kinases ATM/ATR and their targets checkpoint kinases Chk1 and Chk2. By phosphorylating downstream effectors such as p53 and Cdc25 phosphatases, Chk1/Chk2 spread damage signal and ..
  4. ENZYMOLOGY OF REPLICATION OF YEAST CHROMOSOMAL DNA
    Peter M Burgers; Fiscal Year: 2012
    ..onto DNA with the sensor kinase Mec1 (human ATR), activates Mec1 to phosphorylate downstream targets including Rad53 (human Chk1/2)...
  5. PROBES FOR CYTOMETRY
    Zbigniew Darzynkiewicz; Fiscal Year: 2013
    ..antibodies and multiparameter cytometry to measure phosphorylation/activation of key DDRs: histone H2AX, ATM, Chk2 and p53...
  6. A Novel Pathway Involving ATM, PP1 and I-2
    Sankar Mitra; Fiscal Year: 2012
    ..Further, we found Brca1, Cdc7, and Chk2 presented in a complex with the phosphorylated form of I-2...
  7. Protein Kinase Signaling and Cell Cycle Control
    Michael B Yaffe; Fiscal Year: 2013
    ..to genotoxic stress, cells activate two canonical protein kinase pathways, the ATR-Chk1 pathway, and the ATM-Chk2 pathway...
  8. 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. Significantly, the newly identified role of ATF2 in DNA damage response does not require its transcriptional ..
  9. SOMATIC CELL CYCLE REGULATION BY PHOSPHORYLATION
    TONY R HUNTER; Fiscal Year: 2013
    ..The DNA damage response pathway involves activation of a series of protein kinases, including ATM, ATR, and Chk1/Chk2. To learn more about the network of events downstream of DNA damage, we will use SILAC labeling, phosphoprotein/..
  10. Regulatory networks in DNA damage checkpoint response
    KATSONURI SUGIMOTO; Fiscal Year: 2013
    ..Phosphorylated Rad9 interacts with the Rad53 kinase, and the Rad9-Rad53 interaction increases Rad53 kinase activity...
  11. RESTMD-CHARMM simulation of the Chk2/PP2A interaction in DNA repair
    SHANADEEN C BEGAY; Fiscal Year: 2011
    ..to simulate conformational changes caused by phosporylation during the interaction of cell cycle checkpoint kinase, CHK2), with Protein Phosphatase 2A (PP2A) to elucidate signaling mechanisms during the DMA damage response...
  12. Molecular Targeting of the Survivin Pathway in Cancer
    Dario C Altieri; Fiscal Year: 2010
    ..Emphasis will be placed on the role of the checkpoint kinase Chk2 in the regulation of mitochondrial survivin dynamics with respect to p53 requirements, recruitment of proapoptotic ..
  13. Checkpoints and double strand breaks in S. pombe meiosis
    Susan L Forsburg; Fiscal Year: 2013
    ..Indeed, the S phase checkpoint kinase Cds1 (ScRad53) and the replication kinase Hsk1 and its subunit Dfp1 (ScCdc7, ScDbf4) which normally preserve replication ..
  14. Genetics of Meiosis and Recombination in Mice
    John C Schimenti; Fiscal Year: 2013
    ..We identified checkpoint kinase 2 (CHK2;CHEK2) as an essential component of this response...
  15. Cell cycle checkpoint defects lead to chronic inflammation in RA
    Thomas M Aune; Fiscal Year: 2013
    ..To test this hypothesis, we will determine the extent to which this molecular and cellular phenotype is present in HLA-DRB1*04 positive and negative subjects with and without rheumatoid arthritis. ..
  16. Functional analysis of Chk2 in DNA damage response
    Jun Hyun Kim; Fiscal Year: 2013
    ..Extensive analyses of Chk2 and Rad53 (yeast Chk2 ortholog) have highlighted the important roles of Chk2 in S phase...
  17. KINASE ACTIVATION IN THE DNA DAMAGE CHECKPOINTS
    Peter M Burgers; Fiscal Year: 2013
    ..A second protein kinase, Rad53, which is related to human Chk1 and Chk2, acts downstream in halting the cell cycle and activating other response ..
  18. Environmental exposure: Susceptibility alleles in a DNA damage response pathway
    Peter J Stambrook; Fiscal Year: 2013
    ..We will also ask whether such variants are over-represented in women who have had defined radiation exposure and now have developed breast cancer. ..
  19. The role of BRCA1 in nonhomologous repair of chromosomal double-strand breaks
    Fen Xia; Fiscal Year: 2010
    ..Through functional interaction with other DNA damage signaling and repair proteins including Chk2, Mre11 and Ku80, BRCA1 may orchestrate the repair of DSBs by competing mechanisms of homologous recombination (HR) ..
  20. The Mechanism of Spindle Assembly Checkpoint Control in DNA Damage Response
    Yuko Nakajima; Fiscal Year: 2013
    ..formation will be analyzed using molecular markers for SAC activity (Mad1 phosphorylation) and for DDC activity (Rad53 and Chk1 phosphorylation)...
  21. Radiation-Induced G1 Checkpoint Arrest in Yeast
    Stephen J Kron; Fiscal Year: 2010
    ..Our recent studies have linked activation of Rad9 and Rad53 to Rad9 assembly onto chromatin at sites of DNA damage, mediated by recognition of two specific chromatin marks, ..
  22. Chromatin structure and BRCA1 Checkpoint Function
    Roger A Greenberg; Fiscal Year: 2010
    ..BRCA1 is phosphorylated in response to DNA damage by the breast cancer suppressor checkpoint kinases ATM and CHK2, bolstering the concept that a BRCA1 dependent pathway of DNA repair is required to suppress malignancy...
  23. Activating liver carcinogens in yeast by expressing CYP450 polymorphisms
    MICHAEL THOMAS FASULLO; Fiscal Year: 2010
    ..induction of DNA repair genes after AFB1 exposure, and AFB1-associated activation of the checkpoint gene Rad53 (CHK2)...
  24. Bmi-1, a potential therapeutic target in ovarian cancer
    Resham Bhattacharya; Fiscal Year: 2013
    ..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...
  25. Targeting the DNA damage response pathway for the treatment of HSV esophagitis
    Oleg Alekseev; Fiscal Year: 2013
    ..Furthermore, in neurons, which lack nuclear ATM and Chk2 and are incapable of mounting a DDR, HSV-1 infection is typically latent...
  26. Genetic Analysis of MSM Protein Function in S. Pombe
    Susan L Forsburg; Fiscal Year: 2012
    ..evidence that the MCM complex, and particularly Mcm4, is a substrate of the replication checkpoint kinase Cds1. It analyzes mutant forms of Mcm4 that disrupt checkpoint response for their effects on protein recruitment and ..
  27. New determinants of the DNA damage response in the fission yeast S. pombe
    MATTHEW J O'CONNELL; Fiscal Year: 2013
    ..checkpoint is activated when the progression of DNA replication is impeded, and though its effector kinase Cds1, the stability of stalled replication forks is maintained to facilitate resumption of DNA replication...
  28. Cellular Stress Response Signaling Pathways
    MICHAEL BARRY KASTAN; Fiscal Year: 2013
    ..Preliminary data now also implicate the ATM and Chk2 kinases and the HuR translational regulatory protein in this pathway...
  29. MITOCHONDRIAL MOTILITY AND INHERITANCE
    Liza A Pon; Fiscal Year: 2013
    ..We also find that Rad53p, the yeast homologue of the tumor suppressor and the DNA damage checkpoint kinase Chk2, regulates G1 to S progression in response to loss of mtDNA...
  30. Connections and redundancy in the BRCA1-BRCA2 pathway of homologous recombination
    Simon N Powell; Fiscal Year: 2013
    ..BRCA1 is activated to promote homologous recombination by a critical post-translational modification by Chk2 on serine 988, which then results in controlling the extent of 5'-end resection at double- strand breaks...
  31. Function and Regulation of MDMX
    Jiandong Chen; Fiscal Year: 2013
    ..DNA damage induces MDMX phosphorylation by ATM and Chk2, leading to its degradation by MDM2...
  32. The Role of Caspase Activation in the Differentiation-Dependent Life Cycle of HPV
    Cary A Moody; Fiscal Year: 2012
    ..which is necessary for efficient viral genome amplification, as well as caspase activation through the ATM target Chk2. Based on the finding that caspase activation, as well as Chk2 activation, can be stimulated by both E6 and E7, and ..
  33. Tumor suppressor qualities and mechanisms of LZAP activity
    Wendell G Yarbrough; Fiscal Year: 2013
    ..mediated, at least in part, by LZAP abrogation of the G2/M checkpoint through binding and inhibition of Chk1 and Chk2. Human tumor and xenograft mouse tumor data, as well as, LZAP activities as an activator of p53 and suppressor of ..
  34. 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 of Mdm2 ..
  35. Mitotic Response to DNA damage
    WILLIAM EDWARD THEURKAUF; Fiscal Year: 2010
    ..Further, this mitotic damage response required the Chk2 kinase tumor suppressor homologue, and Chk2 localizes to centrosomes, chromosomes, and the midbody...
  36. Host pathways regulating Epstein-Barr virus-mediated B cell growth transformation
    MICAH ALAN LUFTIG; Fiscal Year: 2013
    ..First, we will determine the critical effectors of the ATM/Chk2 dependent DDR detected early after EBV infection...
  37. Therapeutic targeting of stratifin structure and function
    Jian Ting Zhang; Fiscal Year: 2013
    ..in cellular response to radiation-induced apoptosis;(2) to determine if increased stratifin expression regulates Chk2 which, in turn, regulates cell cycle checkpoint for DNA repair and survival;(3) to determine the mechanism of ..
  38. DNA Damage-Response Defects in Prostate Cancer Risk
    Wanguo Liu; Fiscal Year: 2010
    ..Indeed, we have demonstrated that germline mutations in CHK2 and p53AIP1 diminish their capacities to respond to DNA damage and increased prostate cancer risk, but more ..
  39. The role of DNA polymerase eta in DNA damage response and p53 activation
    Xinbin Chen; Fiscal Year: 2013
    ..Furthermore, we found that PolH modulates DNA damage response via the ATM- ChK2-p53 pathway...
  40. Regulation of histone genes upon replication arrest and DNA damage
    HYERYUN PAIK; Fiscal Year: 2007
    ..We have discovered that the essential DNA damage checkpoint kinase Rad53 (the budding yeast homolog of the human tumor suppressor Chk2) is necessary for histone gene regulation following ..
  41. HPV and the DNA Damage Response
    Laimonis A Laimins; Fiscal Year: 2013
    ..The ATM pathway appears to be linked to caspase activation as inhibitors of Chk2 block caspase cleavage...
  42. DNA Damage Checkpoints
    Thanos Halazonetis; Fiscal Year: 2005
    ..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...
  43. Role of 53BP1 during the DNA damage response
    PHILLIP CARPENTER; Fiscal Year: 2006
    ..checkpoint genes including ATM (mutated in ataxia telangiectasia), BRCA1 (Breast cancer gene 1), p53, NBS1, and CHK2. Given the complexity of the cellular response to DNA damaging agents, there will undoubtedly be newly uncovered ..
  44. DNA damage response and DDB
    Pradip Raychaudhuri; Fiscal Year: 2009
    ..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...
  45. Mechanisms of Ischemic Kidney Injury and Repair
    JOSEPH VINCENT BONVENTRE; Fiscal Year: 2013
    ..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...
  46. Phenotypic Plasticity and Inter-Species Communication in Candida Albicans
    STEPHEN KNOX JONES; Fiscal Year: 2013
    ..I hypothesize that the thioredoxin pathway and Rad53 pathways are involved, so they will be tested using gene deletion and over-expression strains for TRX1, TRR1, CAP1,..
  47. Aurora-A/BTAK/STK15 Oncoprotein in Mitotic Spindle Assembly and Checkpoint Respon
    Subrata Sen; Fiscal Year: 2012
    ..4. Investigate the role of two novel Aurora-A interacting proteins, the Chk2 kinase and the mitochondrial membrane protein MTP18 in the survival of cells and in the activation of mitotic cell ..
  48. A model system to study the tumor suppressor APC
    Mark Peifer; Fiscal Year: 2013
    ..Aim we will determine how APC and its partners act to regulate centrosome migration and thus ensure high fidelity chromosome segregation, and explore how Chk2 and other checkpoint regulators buffer the errors that occur in its absence.
  49. Single Stranded DNA: The Genome's Achilles Heel
    Wenyi Feng; Fiscal Year: 2009
    ..base this hypothesis on the following observations: (1) Saccharomyces cerevisiae replication checkpoint-deficient rad53 mutant cells contain stalled replication forks and accumulate large regions of ssDNA upon treatment with the ..
  50. Biology of CHK2 Kinase In Lung Cancer
    Weixin Wang; Fiscal Year: 2005
    ..An immediate ATM downstream target, CHK2, plays a critical role in cell cycle checkpoint regulation and DNA damage induced apoptosis...
  51. Targeted Development of Platinum Drugs
    Zahid H Siddik; Fiscal Year: 2013
    ..Based on the strong relationship of mutual exclusivity, tumors with wild-type p53 are likely to have defective Chk2 expression, and this defect will impact post-translational modification of p53 that is essential for stabilization ..
  52. Markers and therapeutic strategies for overcoming chemoradiotherapy resistance
    John V Heymach; Fiscal Year: 2013
    ..We have also identified several targets, including telomerase and Chk2, for overcoming radioresistance...
  53. Discovery of New Genes for Inherited Predisposition to Breast Cancer by Exome Seq
    TOMAS D WALSH; Fiscal Year: 2013
    ..Discovery of new breast cancer susceptibility genes will allow prevention strategies to be extended to families for which causal genes are currently unknown. ..
  54. Deregulation of the Ubiquitin/26S Proteasome Pathway in AT cells: Role of ISG15
    SHYAMAL DESAI; Fiscal Year: 2009
    ..ATM is a 370 kDa nuclear Ser/Thr kinase contributing to the regulation of p53, BRCA1, and Chk2 signaling pathways, amongst others, and thus required for progression through mitotic checkpoints, double strand ..
  55. PHOSPHOLIPIDS--MEMBRANE SYNTHESIS & SIGNAL TRANSDUCTION
    William Dowhan; Fiscal Year: 2000
    ..will focus on a central step of phospholipid metabolism catalyzed by the CDP-diacylglycerol (-DAG) synthase (CDS1 gene product) which provides the precursor to the major phospholipids found in all organelles of eukaryotic cells ..
  56. CELLULAR PHARMACOLOGY IN CANCER CHEMOTHERAPY
    William Plunkett; Fiscal Year: 2006
    ..The role of inhibitory phosphorylations of Cdk2 in the regulatory hierarchy involving Cdc25A, Chkl and Chk2 will be defined, and we will evaluate the role of cyclin dependent kinase inhibitors such as p21 with respect to ..
  57. Role of MRK in DNA Damage Response
    Rosamaria Ruggieri; Fiscal Year: 2007
    ..The ATM-Chk2/Chkl-Cdc25A cascade, downstream of the BRCT-motif-containing proteins MCD1, Nbsl and 53BP1, plays an important role ..
  58. Chemoprevention Through Activation of Estrogen Receptor Alpha-Induced Senescence
    Harikrishna Nakshatri; Fiscal Year: 2007
    ..2) Senescence-like growth arrest was accompanied with activation of p53 and the checkpoint kinase Chk2 and induction of the senescence-associated gene Cst1...
  59. Extending Safe and Effective Thrombolysis for Stroke
    David Kent; Fiscal Year: 2005
    ..physicians), we propose to develop a set of tools incorporated into a computer-based decision-support instrument (CDS1) for use in real time...
  60. Role of E2F1 in eugenol-mediated antiproliferative activity in melanoma cells
    Rita Ghosh; Fiscal Year: 2009
    ..We have proposed that following eugenol treatment DNA damage signaling occurs through ATM/chk2 pathway that leads to stabilization of E2F1...
  61. Mechanisms of the Human S-phase DNA Damage Checkpoint
    Jun Qin; Fiscal Year: 2006
    ..One pathway for the activation of S-phase checkpoint is ATM/CHK2/CDC25A, in which ATM/CHK2 regulates the degradation of the cell cycle regulator CDC25A through the poly-..
  62. The role of hBUB1-p53 pathway in genomic stability.
    Sam Thiagalingam; Fiscal Year: 2007
    ..Additionally, despite their lower frequency, mutations in Chk1 and Chk2, upstream modulators of p53, were found in a minority of tumors that lack intra-geneic p53 alterations which ..
  63. Nitrosourea-induced growth arrest and apoptotic pathways
    Kevin Brown; Fiscal Year: 2007
    ..to play a key role in MNNG-induced responses, is required for the ATM-dependent activation of the checkpoint kinase Chk2. We hypothesize that MNNG treatment activates multiple pathways that control cell cycle arrest and apoptosis...