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Checkpoint kinase 2

Chk2, Rad53, CHEK2
In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008] (from NCBI)
Top mentioned proteins: Atm, p53, Iris, CAN, Chk1
Papers using Chk2 antibodies
Coupling of T161 and T14 phosphorylations protects cyclin B-CDK1 from premature activation
Maizels Nancy, In PLoS Genetics, 2010
... following antibodies: anti-Cdk2 (M2) and anti-cyclin A (H432) from Santa-Cruz Biotechnology; anti-Cdk1 (POH1), anti-P-T160-Cdk2, anti-P-T161-Cdk1 and anti-P-T68-Chk2 from Cell Signaling Technologies; anti-Chk2 (clone 7) ...
7-Chloro-6-piperidin-1-yl-quinoline-5,8-dione (PT-262), a novel synthetic compound induces lung carcinoma cell death associated with inhibiting ERK and CDC2 phosphorylation via a p53-independent pathway.
Schneider-Stock Regine, In PLoS ONE, 2007
... (#2661), phospho-SAPK/JNK (Thr183/Tyr185) (#9251), phospho-ERK1/2 (Thr202/Tyr204) (#9106), phospho-p38 MAP kinase (Thr180/Tyr182) (#9211), chk1 (#2345), and chk2 (#2662) antibodies were purchased from Cell Signaling Technology ...
Long-term proliferation of human embryonic stem cell-derived neuroepithelial cells using defined adherent culture conditions.
Kirkpatrick David T., In PLoS ONE, 2005
... -β-actin (Santa Cruz Biotechnology), -Nestin, -γ-H2AX (clone JBW301), -GFAP, -Sox2, -Musashi-1 (Millipore), -RAD51 (EMD Biosciences), -pT68-CHK2 (Cell Signaling), and -ATR (2B5), and ...
Zebrafish as a “biosensor”? Effects of ionizing radiation and amifostine on embryonic viability and development.
Akhtar Asifa, In PLoS Genetics, 2005
... larvae were treated with hydroxyurea (Sigma Aldrich) and the Chk2 inhibitor (Sigma Aldrich) at the indicated concentrations ...
Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair.
Kirkpatrick David T., In PLoS ONE, 2004
... (Thermo Scientific), anti-CHK1 (Santa Cruz), anti-CHK2 (Santa Cruz), anti-phospho-CHK1 (Ser 345) (Cell signaling), anti-phospho-CHK2 (Thr 68) (Cell signaling), anti-γH2AX (Upstate), anti-H2AX (Abcam), ...
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Papers on Chk2
Multigene testing of moderate-risk genes: be mindful of the missense.
Tavtigian et al., Salt Lake City, United States. In J Med Genet, Feb 2016
METHODS: We evaluated rare missense substitutions identified from a mutation screen of ATM, CHEK2, MRE11A, RAD50, NBN, RAD51, RINT1, XRCC2 and BARD1 in 1297 cases of early-onset breast cancer and 1121 controls via scores from Align-Grantham Variation Grantham Deviation (GVGD), combined annotation dependent depletion (CADD), multivariate analysis of protein polymorphism (MAPP) and PolyPhen-2.
CHK2 stability is regulated by the E3 ubiquitin ligase SIAH2.
Calzado et al., Córdoba, Spain. In Oncogene, Feb 2016
UNASSIGNED: The serine threonine checkpoint kinase 2 (CHK2) is a critical protein involved in the DNA damage-response pathway, which is activated by phosphorylation inducing cellular response such as DNA repair, cell-cycle regulation or apoptosis.
SOG1: a master regulator of the DNA damage response in plants.
Yoshiyama, Kyoto, Japan. In Genes Genet Syst, Feb 2016
Arabidopsis thaliana has orthologs of several DDR factors that are present in animals; however, some of the important animal regulators, such as the tumor suppressor p53 and the DDR kinases CHK1 and CHK2, have not been found in plants.
Inner nuclear membrane protein Lem2 facilitates Rad3-mediated checkpoint signaling under replication stress induced by nucleotide depletion in fission yeast.
Xu, Dayton, United States. In Cell Signal, Jan 2016
In Schizosaccharomyces pombe, perturbed replication forks activate the sensor kinase Rad3 (ATR/Mec1), which works cooperatively with mediator Mrc1 and the 9-1-1 checkpoint clamp to phosphorylate the effector kinase Cds1 (CHK2/Rad53).
Identification of genomic aberrations in hemangioblastoma by droplet digital PCR and SNP microarray highlights novel candidate genes and pathways for pathogenesis.
Toren et al., Tel Aviv-Yafo, Israel. In Bmc Genomics, Dec 2015
CONCLUSIONS: Our findings provide the first high-resolution genome-wide view of chromosomal changes in hemangioblastoma and identify 23 candidate genes: EGFR, PRDM16, PTPN11, HOXD11, HOXD13, FLT3, PTCH, FGFR1, FOXP1, GPC3, HOXC13, HOXC11, MKL1, CHEK2, IRF4, GPHN, IKZF1, RB1, HOXA9, and micro RNA, such as hsa-mir-196a-2 for hemangioblastoma pathogenesis.
Centrosomes in the DNA damage response-the hub outside the centre.
Morrison et al., Galway, Ireland. In Chromosome Res, Dec 2015
We discuss how several proteins of the DDR are found at centrosomes, including the ATM, ATR, CHK1 and CHK2 kinases, the BRCA1 ubiquitin ligase complex and several members of the poly(ADP-ribose) polymerase family.
Genetic risk assessment and prevention: the role of genetic testing panels in breast cancer.
Narod et al., Toronto, Canada. In Expert Rev Anticancer Ther, Nov 2015
After BRCA1/2, the prevalence of pathogenic mutations was highest in CHEK2 (1.3%), PALB2 (0.9%) and ATM (0.8%).
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.
de Bono et al., Manchester, United Kingdom. In N Engl J Med, Nov 2015
Next-generation sequencing identified homozygous deletions, deleterious mutations, or both in DNA-repair genes--including BRCA1/2, ATM, Fanconi's anemia genes, and CHEK2--in 16 of 49 patients who could be evaluated (33%).
Genes Associated with Human Cancers: Their Expressions, Features, Functions, and Significance.
Mohan et al., Chennai, India. In Crit Rev Eukaryot Gene Expr, 2014
The CHEK2 and ERBB2 (HER2) genes are commonly found to be associated with carcinomas and sarcomas, whereas the MDM2, MSH2, and MSH6 genes are commonly implicated among carcinomas and lymphomas.
[CHEK2-mutation in Dutch breast cancer families: expanding genetic testing for breast cancer].
Oosterwijk et al., Amsterdam, Netherlands. In Ned Tijdschr Geneeskd, 2014
The 1100delC mutation in the CHEK2-gene may explain the occurrence of breast cancer in about 5% of non-BRCA1/2 families in the Netherlands.
Genetic variants at 6p21, 10q23, 16q21 and 22q12 are associated with esophageal cancer risk in a Chinese Han population.
Jin et al., Taiwan. In Int J Clin Exp Med, 2014
rs4822983 in CHEK2 at 22q12 (OR = 1.361, 95% CI = 1.052-1.762),
Integrated genomic characterization of papillary thyroid carcinoma.
Cancer Genome Atlas Research Network, Bethesda, United States. In Cell, 2014
We observed a low frequency of somatic alterations (relative to other carcinomas) and extended the set of known PTC driver alterations to include EIF1AX, PPM1D, and CHEK2 and diverse gene fusions.
Increased microtubule assembly rates influence chromosomal instability in colorectal cancer cells.
Bastians et al., Göttingen, Germany. In Nat Cell Biol, 2014
This phenotype is induced by overexpression of the oncogene AURKA or by loss of the tumour suppressor gene CHK2, a genetic constitution found in 73% of human colorectal cancers.
Exome sequencing identifies somatic gain-of-function PPM1D mutations in brainstem gliomas.
Yan et al., Beijing, China. In Nat Genet, 2014
PPM1D mutations were truncating alterations in exon 6 that enhanced the ability of PPM1D to suppress the activation of the DNA damage response checkpoint protein CHK2.
Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.
Amos et al., United Kingdom. In Nat Genet, 2014
We identified large-effect genome-wide associations for squamous lung cancer with the rare variants BRCA2 p.Lys3326X (rs11571833, odds ratio (OR) = 2.47, P = 4.74 × 10(-20)) and CHEK2 p.Ile157Thr (rs17879961, OR = 0.38, P = 1.27 × 10(-13)).
Chk2 phosphorylation of survivin-DeltaEx3 contributes to a DNA damage-sensing checkpoint in cancer.
Altieri et al., Philadelphia, United States. In Cancer Res, 2012
findings suggest that Chk2-mediated phosphorylation of survivin-DeltaEx3 contributes to a DNA damage-sensing checkpoint that may affect cancer cell sensitivity to genotoxic therapies
Response to DNA damage of CHEK2 missense mutations in familial breast cancer.
King et al., Seattle, United States. In Hum Mol Genet, 2012
Data suggest that in vivo assay of cellular response to DNA damage by mutant CHEK2 alleles may complement and extend epidemiologic and genetic assessment of their clinical consequences.
[Prevalence of mutations BRCA1 5382insC, and CHEK2 1100delC in the population of Siberian region].
Liakhovich et al., In Genetika, 2012
Higher frequencies of these mutations in the patient group compared to the control sample (1.95 versus 0.25% for BRCA1 5382insC, and 1.78 versus 0.40% for CHEK2 1100delC) were observed, pointing to their association with susceptibility to breast cancer
DNA replication stress differentially regulates G1/S genes via Rad53-dependent inactivation of Nrm1.
Wittenberg et al., Los Angeles, United States. In Embo J, 2012
It was shown that genotoxic stress during S phase specifically induces MBF-regulated genes via direct phosphorylation of Nrm1 by Rad53, the effector checkpoint kinase.
Alternative splicing of CHEK2 and codeletion with NF2 promote chromosomal instability in meningioma.
Johnson et al., Boston, United States. In Neoplasia, 2012
alternative splicing and frequent codeletion of CHEK2 and NF2 contribute to the genomic instability and associated development of aggressive biologic behavior in meningiomas.
More papers using Chk2 antibodies
A peptidomimetic inhibitor of farnesyl:protein transferase blocks the anchorage-dependent and -independent growth of human tumor cell lines
Nie Daotai et al., In Cancer Cell International, 1994
... Phospho-Chk2 (Thr68) was purchased from Cell Signaling Technology, Inc ...
Isolation of Epstein-Barr virus (EBV)-negative cell clones from the EBV-positive Burkitt's lymphoma (BL) line Akata: malignant phenotypes of BL cells are dependent on EBV.
Sugden Bill, In PLoS Pathogens, 1993
... Anti-Phosho-p53 (Ser15), anti-Phosho-p53 (Ser20), anti-Phopho-Chk2 (Thr68) and anti-Cleaved PARP (Asp214) rabbit polyclonal antibodies were obtained from Cell Signaling Technology ...
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