Chek2

Summary

Gene Symbol: Chek2
Description: checkpoint kinase 2
Alias: CHK2, Cds1, HUCDS1, Rad53, serine/threonine-protein kinase Chk2, CHK2 checkpoint homolog, Cds1 homolog, Rad53 homolog, protein kinase Chk2
Species: mouse
Products:     Chek2

Top Publications

  1. Zheng L, Asprodites N, Keene A, Rodriguez P, Brown K, Davila E. TLR9 engagement on CD4 T lymphocytes represses gamma-radiation-induced apoptosis through activation of checkpoint kinase response elements. Blood. 2008;111:2704-13 pubmed
    ..Irradiated, TLR9-engaged cells showed higher levels of phosphorylated Chk1 and Chk2. While the levels of activated ATM in response to IR did not differ between TLR9-stimulated and unstimulated cells, ..
  2. Nalapareddy K, Choudhury A, Gompf A, Ju Z, Ravipati S, Leucht T, et al. CHK2-independent induction of telomere dysfunction checkpoints in stem and progenitor cells. EMBO Rep. 2010;11:619-25 pubmed publisher
    ..Here, we show that CHK2 deletion impairs the induction of senescence in mouse and human fibroblasts...
  3. Stracker T, Couto S, Cordon Cardo C, Matos T, Petrini J. Chk2 suppresses the oncogenic potential of DNA replication-associated DNA damage. Mol Cell. 2008;31:21-32 pubmed publisher
    The Mre11 complex (Mre11, Rad50, and Nbs1) and Chk2 have been implicated in the DNA-damage response, an inducible process required for the suppression of malignancy...
  4. Bolcun Filas E, Rinaldi V, White M, Schimenti J. Reversal of female infertility by Chk2 ablation reveals the oocyte DNA damage checkpoint pathway. Science. 2014;343:533-6 pubmed publisher
    ..Here, we report that checkpoint kinase 2 (Chk2 or Chek2), is essential for culling mouse oocytes bearing unrepaired meiotic or induced DNA double-strand breaks (DSBs)...
  5. Matsuoka S, Huang M, Elledge S. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science. 1998;282:1893-7 pubmed
    ..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...
  6. Takai H, Naka K, Okada Y, Watanabe M, Harada N, Saito S, et al. Chk2-deficient mice exhibit radioresistance and defective p53-mediated transcription. EMBO J. 2002;21:5195-205 pubmed
    The mammalian Chk2 kinase is thought to mediate ATM-dependent signaling in response to DNA damage. The physiological role of mammalian Chk2 has now been investigated by the generation of Chk2-deficient mice...
  7. Bahassi E, Robbins S, Yin M, Boivin G, Kuiper R, van Steeg H, et al. Mice with the CHEK2*1100delC SNP are predisposed to cancer with a strong gender bias. Proc Natl Acad Sci U S A. 2009;106:17111-6 pubmed publisher
    The CHEK2 kinase (Chk2 in mouse) is a member of a DNA damage response pathway that regulates cell cycle arrest at cell cycle checkpoints and facilitates the repair of dsDNA breaks by a recombination-mediated mechanism...
  8. McPherson J, Lemmers B, Hirao A, Hakem A, Abraham J, Migon E, et al. Collaboration of Brca1 and Chk2 in tumorigenesis. Genes Dev. 2004;18:1144-53 pubmed
    ..Here, we show that Chk2 inactivation is partially equivalent to p53 inactivation, in that Chk2 deficiency facilitates the development, ..
  9. Hirao A, Cheung A, Duncan G, Girard P, Elia A, Wakeham A, et al. Chk2 is a tumor suppressor that regulates apoptosis in both an ataxia telangiectasia mutated (ATM)-dependent and an ATM-independent manner. Mol Cell Biol. 2002;22:6521-32 pubmed
    ..b>Chk2 activated by IR contributes to this stabilization, possibly by direct phosphorylation...

More Information

Publications70

  1. Motoyama N, Naka K. DNA damage tumor suppressor genes and genomic instability. Curr Opin Genet Dev. 2004;14:11-6 pubmed
    ..The protein kinases ATM and ATR, as well as their downstream substrates Chk1 and Chk2, are central players in checkpoint activation in response to DNA damage...
  2. Kokavec J, Zikmund T, Savvulidi F, Kulvait V, Edelmann W, Skoultchi A, et al. The ISWI ATPase Smarca5 (Snf2h) Is Required for Proliferation and Differentiation of Hematopoietic Stem and Progenitor Cells. Stem Cells. 2017;35:1614-1623 pubmed publisher
    ..Thus, Smarca5 plays indispensable roles during early hematopoiesis and erythropoiesis. Stem Cells 2017;35:1614-1623. ..
  3. Morales M, Theunissen J, Kim C, Kitagawa R, Kastan M, Petrini J. The Rad50S allele promotes ATM-dependent DNA damage responses and suppresses ATM deficiency: implications for the Mre11 complex as a DNA damage sensor. Genes Dev. 2005;19:3043-54 pubmed
    ..Rad50(S/S) mice exhibit precipitous apoptotic attrition of hematopoietic cells. We generated ATM- and Chk2-deficient Rad50(S/S) mice and found that Rad50(S/S) cellular attrition was strongly ATM and Chk2 dependent...
  4. Keramaris E, Hirao A, Slack R, Mak T, Park D. Ataxia telangiectasia-mutated protein can regulate p53 and neuronal death independent of Chk2 in response to DNA damage. J Biol Chem. 2003;278:37782-9 pubmed
    ..Previous reports have suggested that ATM regulation of p53 occurs through Chk2. However, in our present paradigms, we show that ATM functions separately from Chk2 to regulate p53 stability and ..
  5. Kim S, Cao L, Li C, Xu X, Huber L, Chodosh L, et al. Uterus hyperplasia and increased carcinogen-induced tumorigenesis in mice carrying a targeted mutation of the Chk2 phosphorylation site in Brca1. Mol Cell Biol. 2004;24:9498-507 pubmed
    ..After DNA damage, BRCA1 is phosphorylated by CHK2 at serine 988, followed by a change in its intracellular location...
  6. Chen C, Shimizu S, Tsujimoto Y, Motoyama N. Chk2 regulates transcription-independent p53-mediated apoptosis in response to DNA damage. Biochem Biophys Res Commun. 2005;333:427-31 pubmed
    ..The protein kinase Chk2 is an important regulator of p53 function in mammalian cells exposed to ionizing radiation (IR)...
  7. Miller M, Peter A, Wharton S, Wyllie A. Proliferation and death of conditionally immortalized neural cells from murine neocortex: p53 alters the ability of neuron-like cells to re-enter the cell cycle. Brain Res. 2003;965:57-66 pubmed
    ..Therefore, p53-mediated activities appear to be involved in the proliferation, survival, and post-mitotic nature of neuron-like cells. ..
  8. Miles D, Van Den Bergen J, Wakeling S, Anderson R, Sinclair A, Western P. The proto-oncogene Ret is required for male foetal germ cell survival. Dev Biol. 2012;365:101-9 pubmed publisher
    ..Either way, this study identifies the proto-oncogene RET as a novel component of the foetal male germ cell development pathway. ..
  9. Squatrito M, Brennan C, Helmy K, Huse J, Petrini J, Holland E. Loss of ATM/Chk2/p53 pathway components accelerates tumor development and contributes to radiation resistance in gliomas. Cancer Cell. 2010;18:619-29 pubmed publisher
    ..encoding components of the DDR pathway are frequently altered in human gliomas and that loss of elements of the ATM/Chk2/p53 cascade accelerates tumor formation in a glioma mouse model...
  10. El Ghamrasni S, Pamidi A, Halaby M, Bohgaki M, Cardoso R, Li L, et al. Inactivation of chk2 and mus81 leads to impaired lymphocytes development, reduced genomic instability, and suppression of cancer. PLoS Genet. 2011;7:e1001385 pubmed publisher
    b>Chk2 is an effector kinase important for the activation of cell cycle checkpoints, p53, and apoptosis in response to DNA damage. Mus81 is required for the restart of stalled replication forks and for genomic integrity...
  11. Pines A, Kelstrup C, Vrouwe M, Puigvert J, Typas D, Misovic B, et al. Global phosphoproteome profiling reveals unanticipated networks responsive to cisplatin treatment of embryonic stem cells. Mol Cell Biol. 2011;31:4964-77 pubmed publisher
    ..This study provides an integrated view of pathways activated by genotoxic stress and deciphers kinases that play a pivotal role in regulating cellular processes other than the DNA damage response. ..
  12. Chen C, Chu P, Lee L, Lien H, Lin T, Fan C, et al. Disruption of murine mp29/Syf2/Ntc31 gene results in embryonic lethality with aberrant checkpoint response. PLoS ONE. 2012;7:e33538 pubmed publisher
    ..A lower level of acetylated ?-tubulin was also observed in zfp29 morphants. Together, these results illustrate an indispensable role of mp29 in DNA checkpoint response during embryonic development. ..
  13. Wang C, Huang E, Huang S, Chung B. DNA-PK/Chk2 induces centrosome amplification during prolonged replication stress. Oncogene. 2015;34:1263-9 pubmed publisher
    ..Depletion of DNA-PK abrogated checkpoint kinase (Chk)2 activation and partially reduced Chk1 activation. Chk2 depletion blocked HU-induced centrosome amplification, indicating a function of Chk2 in centrosome amplification...
  14. Matsuki T, Hori G, Furuichi T. Gene expression profiling during the embryonic development of mouse brain using an oligonucleotide-based microarray system. Brain Res Mol Brain Res. 2005;136:231-54 pubmed
    ..Moreover, we identified a novel gene that encodes a putative protein kinase, Ebr kinase, which is differentially expressed in the developing brain. ..
  15. Lee Y, Katyal S, Downing S, Zhao J, Russell H, McKinnon P. Neurogenesis requires TopBP1 to prevent catastrophic replicative DNA damage in early progenitors. Nat Neurosci. 2012;15:819-26 pubmed publisher
    ..Thus, TopBP1 is crucial for maintaining genome integrity in the early progenitors that drive neurogenesis. ..
  16. Qu L, Huang S, Baltzis D, Rivas Estilla A, Pluquet O, Hatzoglou M, et al. Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3beta. Genes Dev. 2004;18:261-77 pubmed
    ..It is concluded that inactivation of p53 is a protective mechanism utilized by cells to adapt to ER stress. ..
  17. Foster S, De S, Johnson L, Petrini J, Stracker T. Cell cycle- and DNA repair pathway-specific effects of apoptosis on tumor suppression. Proc Natl Acad Sci U S A. 2012;109:9953-8 pubmed publisher
    ..Previously, we have shown that the Chk2 kinase functions independently of the Mre11 complex (Mre11, Rad50, and Nbs1) and ATM in apoptosis and suppresses ..
  18. Rinaldi V, Bolcun Filas E, Kogo H, Kurahashi H, Schimenti J. The DNA Damage Checkpoint Eliminates Mouse Oocytes with Chromosome Synapsis Failure. Mol Cell. 2017;67:1026-1036.e2 pubmed publisher
    ..Here we show that the CHK2 (CHEK2)-dependent DNA damage checkpoint culls not only recombination-defective mouse oocytes but also SPO11-deficient ..
  19. García Beccaria M, Martinez P, Flores J, Blasco M. In vivo role of checkpoint kinase 2 in signaling telomere dysfunction. Aging Cell. 2014;13:810-6 pubmed publisher
    Checkpoint kinase 2 (CHK2) is a downstream effector of the DNA damage response (DDR)...
  20. Dong D, Yu J, Wu Y, Fu N, Villela N, Yang P. Maternal diabetes triggers DNA damage and DNA damage response in neurulation stage embryos through oxidative stress. Biochem Biophys Res Commun. 2015;467:407-12 pubmed publisher
    ..X) and DDR signaling intermediates, including phosphorylated checkpoint 1 (p-Chk1), phosphorylated checkpoint 2 (p-Chk2), and p53...
  21. Zhao T, Tang X, Umeshappa C, Ma H, Gao H, Deng Y, et al. Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF-κB-Regulated Anti-Apoptosis and p53/PCNA- and ATM/ATR-Chk1/2-Controlled DNA-Damage Response Pathways. J Cell Biochem. 2016;117:2138-48 pubmed publisher
    ..J. Cell. Biochem. 117: 2138-2148, 2016. © 2016 Wiley Periodicals, Inc. ..
  22. Sheikh M, Malik Y, Zhu X. RA-Induced Transcriptional Silencing of Checkpoint Kinase-2 through Promoter Methylation by Dnmt3b Is Required for Neuronal Differentiation of P19 Cells. J Mol Biol. 2017;429:2463-2473 pubmed publisher
    ..The present study describes the regulation of expression and function of checkpoint kinase (Chk2), which was one of the target genes of Dnmt3b...
  23. Yang S, Jeong J, Brown A, Lee C, Pandolfi P, Chung J, et al. Promyelocytic leukemia activates Chk2 by mediating Chk2 autophosphorylation. J Biol Chem. 2006;281:26645-54 pubmed
    b>Chk2 is a kinase critical for DNA damage-induced apoptosis and is considered a tumor suppressor. Chk2 is essential for p53 transcriptional and apoptotic activities...
  24. Elliott E, Sheaffer K, Schug J, Stappenbeck T, Kaestner K. Dnmt1 is essential to maintain progenitors in the perinatal intestinal epithelium. Development. 2015;142:2163-72 pubmed publisher
    ..These results demonstrate an essential role for Dnmt1 in maintaining genomic stability during intestinal development and the establishment of intestinal crypts. ..
  25. Fahkri H, Zhang B, Fajol A, Hernando N, Elvira B, Mannheim J, et al. Checkpoint kinase Chk2 controls renal Cyp27b1 expression, calcitriol formation, and calcium-phosphate metabolism. Pflugers Arch. 2015;467:1871-80 pubmed publisher
    Checkpoint kinase 2 (Chk2) is the main effector kinase of ataxia telangiectasia mutated (ATM) and responsible for cell cycle regulation...
  26. Joe Y, Jeong J, Yang S, Kang H, Motoyama N, Pandolfi P, et al. ATR, PML, and CHK2 play a role in arsenic trioxide-induced apoptosis. J Biol Chem. 2006;281:28764-71 pubmed
    ..We find that ATO induces apoptosis, at least in part, by activating proapoptotic kinase Chk2. ATO does this by stimulating ATR (ataxia telangiectasia mutated and Rad3-related) kinase, a Chk2-activating kinase...
  27. Luo Y, Schimenti J. MCM9 deficiency delays primordial germ cell proliferation independent of the ATM pathway. Genesis. 2015;53:678-84 pubmed publisher
    ..This reduction was attributable to reduced proliferation, not apoptosis, and this response was independent of ATM-CHK2-TRP53-P21 signaling...
  28. Yu T, Wang P, Rao J, Zou T, Liu L, Xiao L, et al. Chk2-dependent HuR phosphorylation regulates occludin mRNA translation and epithelial barrier function. Nucleic Acids Res. 2011;39:8472-87 pubmed publisher
    ..HuR association with the occludin mRNA depended on Chk2-dependent HuR phosphorylation...
  29. Pacheco S, Marcet Ortega M, Lange J, Jasin M, Keeney S, Roig I. The ATM signaling cascade promotes recombination-dependent pachytene arrest in mouse spermatocytes. PLoS Genet. 2015;11:e1005017 pubmed publisher
    ..ATM activity is attenuated by hypomorphic mutations in Mre11 or Nbs1 or by elimination of the ATM-effector kinase CHK2. These mutant backgrounds nonetheless experience an apoptotic block to further spermatogenic progression, most ..
  30. Bahassi E, Penner C, Robbins S, Tichy E, Feliciano E, Yin M, et al. The breast cancer susceptibility allele CHEK2*1100delC promotes genomic instability in a knock-in mouse model. Mutat Res. 2007;616:201-9 pubmed
    Allelic variants of CHEK2 contribute to an elevated risk for human breast cancer and possibly other cancer types...
  31. Koczor C, Shokolenko I, Boyd A, Balk S, Wilson G, LeDoux S. Mitochondrial DNA damage initiates a cell cycle arrest by a Chk2-associated mechanism in mammalian cells. J Biol Chem. 2009;284:36191-201 pubmed publisher
    ..Furthermore, mechanistic studies showed that Chk2 phosphorylation was enhanced following menadione exposure...
  32. Jack M, Woo R, Hirao A, Cheung A, Mak T, Lee P. Chk2 is dispensable for p53-mediated G1 arrest but is required for a latent p53-mediated apoptotic response. Proc Natl Acad Sci U S A. 2002;99:9825-9 pubmed
    ..The checkpoint kinase, Chk2, has been implicated in both of these responses and is believed to function in an ataxia telangiectasia (Atm)-..
  33. MacLaren A, Slavin D, McGowan C. Chk2 protects against radiation-induced genomic instability. Radiat Res. 2009;172:463-72 pubmed publisher
    The murine Chk2 kinase is activated after exposure to ionizing radiation and is necessary for p53-dependent apoptosis, but the role Chk2 plays in determining genomic stability is poorly understood...
  34. Zaugg K, Su Y, Reilly P, Moolani Y, Cheung C, Hakem R, et al. Cross-talk between Chk1 and Chk2 in double-mutant thymocytes. Proc Natl Acad Sci U S A. 2007;104:3805-10 pubmed
    ..Strikingly, loss of Chk1 activated the checkpoint kinase Chk2 as well as the tumor suppressor p53 in these thymocytes...
  35. Höglund A, Strömvall K, Li Y, Forshell L, Nilsson J. Chk2 deficiency in Myc overexpressing lymphoma cells elicits a synergistic lethal response in combination with PARP inhibition. Cell Cycle. 2011;10:3598-607 pubmed publisher
    ..These, in turn, activate the DNA damage transducers Chk1 and Chk2. Here, we show that Myc can stimulate Chek2 transcript indirectly in vitro as well as in B cells of ?-Myc transgenic mice or in the intestine of Apc (Min) ..
  36. Pabla N, Huang S, Mi Q, Daniel R, Dong Z. ATR-Chk2 signaling in p53 activation and DNA damage response during cisplatin-induced apoptosis. J Biol Chem. 2008;283:6572-83 pubmed
    ..Downstream of ATR, both Chk1 and Chk2 are phosphorylated during cisplatin treatment in an ATR-dependent manner...
  37. Chou W, Wang H, Wong F, Ding S, Wu P, Shieh S, et al. Chk2-dependent phosphorylation of XRCC1 in the DNA damage response promotes base excision repair. EMBO J. 2008;27:3140-50 pubmed publisher
    ..Ataxia telangiectasia-mutated (ATM)-checkpoint kinase 2 (Chk2) and ATM- and Rad3-related (ATR)-Chk1, triggered, respectively, by DNA double-strand breaks and blocked replication ..
  38. Khoury Haddad H, Guttmann Raviv N, Ipenberg I, Huggins D, Jeyasekharan A, Ayoub N. PARP1-dependent recruitment of KDM4D histone demethylase to DNA damage sites promotes double-strand break repair. Proc Natl Acad Sci U S A. 2014;111:E728-37 pubmed publisher
    ..Altogether, our findings implicate KDM4D in DDR, furthering the links between the cancer-relevant networks of epigenetic regulation and genome stability...
  39. Zhu Y, Demidov O, Goh A, Virshup D, Lane D, Bulavin D. Phosphatase WIP1 regulates adult neurogenesis and WNT signaling during aging. J Clin Invest. 2014;124:3263-73 pubmed publisher
    ..We propose that WIP1 controls DKK3-dependent inhibition of neuronal differentiation during aging and suggest that regulating WIP1 levels could prevent certain aspects of functional decline of the aging brain. ..
  40. Jack M, Woo R, Motoyama N, Takai H, Lee P. DNA-dependent protein kinase and checkpoint kinase 2 synergistically activate a latent population of p53 upon DNA damage. J Biol Chem. 2004;279:15269-73 pubmed
    The role of the checkpoint kinase 2 (Chk2) as an upstream activator of p53 following DNA damage has been controversial...
  41. Pirouz M, Pilarski S, Kessel M. A critical function of Mad2l2 in primordial germ cell development of mice. PLoS Genet. 2013;9:e1003712 pubmed publisher
    ..Together, these results demonstrate the potential of Mad2l2 in the regulation of both cell cycle and the epigenetic status. The function of Mad2l2 is essential in PGCs, and thus of high relevance for fertility. ..
  42. Powers J, Hong S, Mayhew C, Rogers P, Knudsen E, Johnson D. E2F1 uses the ATM signaling pathway to induce p53 and Chk2 phosphorylation and apoptosis. Mol Cancer Res. 2004;2:203-14 pubmed
    ..Moreover, E2F1 induces ATM- and NBS1-dependent phosphorylation of the checkpoint kinase Chk2 at Thr68, a phosphorylation site that stimulates Chk2 activity...
  43. Demidov O, Zhu Y, Kek C, Goloudina A, Motoyama N, Bulavin D. Role of Gadd45a in Wip1-dependent regulation of intestinal tumorigenesis. Cell Death Differ. 2012;19:1761-8 pubmed publisher
    ..We propose that silencing of Gadd45a is sufficient to override p53 activation in the presence of active ?-catenin under conditions of an enhanced DNA damage response. ..
  44. Enriquez Rios V, Dumitrache L, Downing S, Li Y, Brown E, Russell H, et al. DNA-PKcs, ATM, and ATR Interplay Maintains Genome Integrity during Neurogenesis. J Neurosci. 2017;37:893-905 pubmed publisher
    ..These data demonstrate functionally distinct, but cooperative, roles for each kinase in preserving genome stability in the nervous system. ..
  45. Finnberg N, Gokare P, Navaraj A, Lang Kuhs K, Cerniglia G, Yagita H, et al. Agonists of the TRAIL Death Receptor DR5 Sensitize Intestinal Stem Cells to Chemotherapy-Induced Cell Death and Trigger Gastrointestinal Toxicity. Cancer Res. 2016;76:700-12 pubmed publisher
    ..Interestingly, our data also indicated that genetic or pharmacologic targeting of Chk2 may counteract GIT without negatively affecting the antitumor responses of combined DR5 agonist/chemotherapy ..
  46. Ullah Z, de Renty C, DePamphilis M. Checkpoint kinase 1 prevents cell cycle exit linked to terminal cell differentiation. Mol Cell Biol. 2011;31:4129-43 pubmed publisher
    ..Thus, CHK1 is part of a "G2 restriction point" that prevents premature cell cycle exit in cells programmed for terminal differentiation, a role that CHK2 cannot play.
  47. Dai X, Duan X, Liu H, Cui X, Kim N, Sun S. Chk2 regulates cell cycle progression during mouse oocyte maturation and early embryo development. Mol Cells. 2014;37:126-32 pubmed publisher
    As a tumor suppressor homologue during mitosis, Chk2 is involved in replication checkpoints, DNA repair, and cell cycle arrest, although its functions during mouse oocyte meiosis and early embryo development remain uncertain...
  48. Hirao A, Kong Y, Matsuoka S, Wakeham A, Ruland J, Yoshida H, et al. DNA damage-induced activation of p53 by the checkpoint kinase Chk2. Science. 2000;287:1824-7 pubmed
    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...
  49. Lee I, Kawai Y, Fergusson M, Rovira I, Bishop A, Motoyama N, et al. Atg7 modulates p53 activity to regulate cell cycle and survival during metabolic stress. Science. 2012;336:225-8 pubmed publisher
    ..Inhibition of the DNA damage response by deletion of the protein kinase Chk2 partially rescued postnatal lethality in Atg7(-/-) mice...
  50. Cao L, Xu X, Bunting S, Liu J, Wang R, Cao L, et al. A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiency. Mol Cell. 2009;35:534-41 pubmed publisher
    ..These observations may have important implications for Brca1-mediated tumor formation as well as for the molecular pathway leading from genomic instability to organismal aging. ..
  51. Lee Y, Brown E, Chang S, McKinnon P. Pot1a prevents telomere dysfunction and ATM-dependent neuronal loss. J Neurosci. 2014;34:7836-44 pubmed publisher
    ..These data reveal that neural cell loss after DNA damage selectively engages Atm signaling, highlighting how specific DNA lesions can dictate neuropathology arising in human neurodegenerative syndromes. ..
  52. Bohgaki M, Hakem A, Halaby M, Bohgaki T, Li Q, Bissey P, et al. The E3 ligase PIRH2 polyubiquitylates CHK2 and regulates its turnover. Cell Death Differ. 2013;20:812-22 pubmed publisher
    The serine threonine kinase checkpoint kinase 2 (CHK2) is a DNA damage checkpoint protein important for the ATM-p53 signaling pathway...
  53. Li T, Wang Z. Point mutation at the Nbs1 Threonine 278 site does not affect mouse development, but compromises the Chk2 and Smc1 phosphorylation after DNA damage. Mech Ageing Dev. 2011;132:382-8 pubmed publisher
    ..Ionizing radiation (IR) of primary Nbs1(T278A) MEFs reveals no obvious defects in the Chk2 phosphorylation at 1Gy, but a delayed phosphorylation of Chk2 and Smc1 only at intermediate (4...
  54. Liu J, Cao L, Chen J, Song S, Lee I, Quijano C, et al. Bmi1 regulates mitochondrial function and the DNA damage response pathway. Nature. 2009;459:387-392 pubmed publisher
    ..the antioxidant N-acetylcysteine or genetic disruption of the DNA damage response pathway by Chk2 (also known as Chek2) deletion...
  55. Gupta G, Vanness K, Barlas A, Manova Todorova K, Wen Y, Petrini J. The Mre11 complex suppresses oncogene-driven breast tumorigenesis and metastasis. Mol Cell. 2013;52:353-65 pubmed publisher
    ..These findings provide insight into the mechanism of DDR engagement by activated oncogenes and highlight genetic interactions between the DDR and Ink4a-Arf pathways in suppression of oncogene-driven tumorigenesis and metastasis. ..
  56. Meyer S, Peace B, Bahassi E, Kavanaugh G, Wagh P, Robbins S, et al. Chk2*1100delC Acts in synergy with the Ron receptor tyrosine kinase to accelerate mammary tumorigenesis in mice. Cancer Lett. 2010;296:186-93 pubmed publisher
    The CHEK2 (Chk2 in mice) polymorphic variant, CHEK2*1100delC, leads to genomic instability and is associated with an increased risk for breast cancer...
  57. Niida H, Murata K, Shimada M, Ogawa K, Ohta K, Suzuki K, et al. Cooperative functions of Chk1 and Chk2 reduce tumour susceptibility in vivo. EMBO J. 2010;29:3558-70 pubmed publisher
    Although the linkage of Chk1 and Chk2 to important cancer signalling suggests that these kinases have functions as tumour suppressors, neither Chk1+/- nor Chk2-/- mice show a predisposition to cancer under unperturbed conditions...
  58. Cao L, Kim S, Xiao C, Wang R, Coumoul X, Wang X, et al. ATM-Chk2-p53 activation prevents tumorigenesis at an expense of organ homeostasis upon Brca1 deficiency. EMBO J. 2006;25:2167-77 pubmed
    ..Here, we show that reduced expression and/or the absence of Chk2 allow Brca1(delta11/delta11) mice to escape from embryonic lethality...
  59. Jankovic M, Robbiani D, Dorsett Y, Eisenreich T, Xu Y, Tarakhovsky A, et al. Role of the translocation partner in protection against AID-dependent chromosomal translocations. Proc Natl Acad Sci U S A. 2010;107:187-92 pubmed publisher
    ..We conclude that AID-induced double-strand breaks in non-Ig genes other than c-myc lead to their translocation, and that at least two nonoverlapping pathways protect against translocations in primary B cells. ..
  60. Bruno T, De Nicola F, Iezzi S, Lecis D, D Angelo C, Di Padova M, et al. Che-1 phosphorylation by ATM/ATR and Chk2 kinases activates p53 transcription and the G2/M checkpoint. Cancer Cell. 2006;10:473-86 pubmed
    ..The checkpoint kinases ATM/ATR and Chk2 interact with Che-1 and promote its phosphorylation and accumulation in response to DNA damage...
  61. Louria Hayon I, Grossman T, Sionov R, Alsheich O, Pandolfi P, Haupt Y. The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation. J Biol Chem. 2003;278:33134-41 pubmed
    ..of Mdm2 by prolonging the stress-induced phosphorylation of p53 on serine 20, a site of the checkpoint kinase 2 (Chk2). PML recruits Chk2 and p53 into the PML nuclear bodies and enhances p53/Chk2 interaction...