It is proposed that autophosphorylation of Chk2 may contribute to Chk2 activation.
Chk2 molecular interaction map and rationale for Chk2 inhibitors.
Promyelocytic leukemia activates Chk2 by mediating Chk2 autophosphorylation.
CHK2 kinase--a busy messenger.
CHK2: a tumor suppressor or not?
Analysis of CHK2 in vulval neoplasia.
Chk2 leaves the PML depot.
The Chk2 protein kinase.
The regulation of CHK2 in human cancer.
Collaboration of Brca1 and Chk2 in tumorigenesis.
Role of CHK2 in cancer development.
ATR dependent activation of Chk2.
To investigate the role of Chk2 in multicellular organisms, a Drosophila chk2 (Dmchk2) mutant was generated.
Chk2 can cross-phosphorylate another Chk2 molecule in an oligomeric complex.
Total Chk2 and Chk2 Thr68 are also hyperphosphorylated in the presence of caffeine.
Characterization of tumor-associated Chk2 mutations.
Analysis of the CHK2 gene in lymphoid malignancies.
Mutations of Chk2 in primary hematopoietic neoplasms.
This death response is independent of p53 and Chk2.
Analysis of CHK2 in patients with myelodysplastic syndromes.
Chk2 activation and phosphorylation-dependent oligomerization.
Endogenous Chk2 coimmunoprecipitates Ku70 and Ku80.
Chk2 meets Plk3 in damage control.
CHK2-dependent phosphorylation of BRCA1 in hypoxia.
Chk2 appeared not to be involved in the Cdk1 inhibition.
CHK2 is known to phosphorylate and stabilize p53.
Chk2 mediates RITA-induced apoptosis.
EAPP modulates the activity of p21 and Chk2.
Chk2 forms oligomers that minimally require the FHA domain of one Chk2 molecule and the SCD within another Chk2 molecule.
Interestingly, the induction depends on CHK2 because CHK2-targeting small interfering RNA or a CHK2 inhibitor abolishes the increase.
To characterize the localization of CHK2, we generated cells expressing inducible GFP-CHK2 and Flag-CHK2 fusion proteins.
Moreover, the S516A mutant of Chk2 is defective in ionizing radiation-induced apoptosis, suggesting that Chk2 autophosphorylation is critical for Chk2 function following DNA damage.
A kinase-inactive mutant of Chk2 was phosphorylated on T68 and T383/T387 but not on S516 in cells containing Chk2 and on T68 but not T383/T387 or S516 in cells lacking Chk2.
The absent CHK2 expression in NSCLC was due to hypermethylation of the CHK2 gene promoter, preventing from binding of a transcriptional factor, leading to silence of the CHK2 gene transcription.
The chk2 homologue gene (Eh chk2) was expected to encode 398 amino acids and showed nearly 50% homology to human Chk2 in amino acid sequence.
To further establish the involvement of Chk2 in DIM-mediated G(2)/M arrest, cells were transfected with dominant-negative Chk2 (DN-Chk2).
Also, the synergism was independent of Chk2 both in Chk2-complemented cells and Chk2 knockout cells, suggesting additional mechanisms for cell-cycle abrogation by AZD7762.
To this end, we generated mice doubly deficient for Chk2 and either Terc (Chk2(-/-) Terc(-/-) ) or Trf1 (Trf1(Delta/Delta) K5Cre Chk2(-/-) ).
Thus, Chk2 may be inactivated by multiple mechanisms in the cell.
Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro.
Likewise, Hus1 was dispensable for genotoxin-induced Chk2 phosphorylation.
Chk2 activation dependence on Nbs1 after DNA damage.
A Chk2-like gene was identified in the genome of Caenorhabditis elegans.
Determination of substrate specificity and putative substrates of Chk2 kinase.
Absence of germline CHK2 mutations in familial gastric cancer.
There were no FGC cases that showed germline CHK2 mutations.
Conflicting evidence implicates Chk2 as an inhibitor or promoter of apoptosis.
A characteristic of the ATM-Chk2 pathway is its redundancy.
We will review the short list of published Chk2 inhibitors.
Novel non-benzimidazole chk2 kinase inhibitors.
HDM2 negatively affects the Chk2-mediated phosphorylation of p53.
HDM2 itself is only slightly phosphorylated by Chk2.
Establishment of a cell-free system to study the activation of Chk2.
This method will be useful for identification of cofactors required for activation of Chk2.
Chk1 and Chk2 kinases in checkpoint control and cancer.
Chk2 phosphorylates and stabilizes p53 in response to ionizing radiation.
p53 has been reported as another substrate of Chk2.
Furthermore, ectopic expression Chk2 activates cellular Plk3.
Drug discovery targeting Chk1 and Chk2 kinases.
Concomitant inactivation of p53 and Chk2 in breast cancer.
In contrast, Chk2 does not phosphorylate p73alpha in vitro.
Moreover, the regulatory domain of CHK2, but not that of CHK1, can oligomerize.
CHK2 kinase expression was known to be ubiquitous in mammalian cells.
The DNA damage checkpoint is mediated by the Chk2/Cds1 kinase.
Aberrations of the CHK2 gene are rare in pediatric solid tumors.
Regulation of CHK2 by DNA-dependent protein kinase.
DNA enhances the Chk2 phosphorylation by cellular fractions in vitro.
Chk2 is phosphorylated by purified DNA-PK in vitro.
One of the kinase genes was a homologue of human chk2 gene.
Chk2 also stimulates MDMX ubiquitination and degradation by MDM2.
Phosphorylation of S342 and S367 in vivo require the Chk2 kinase.
Chk2 may be the ancestral regulator of p53 function.
Telomere attrition and Chk2 activation in human heart failure.
Plk1 overexpression enhances phosphorylation of Chk2 at Thr-68.
Insight into Chk2 has derived from multiple approaches.
Checking in on Cds1 (Chk2): A checkpoint kinase and tumor suppressor.
Furthermore, inactivation of Chk2 and Brca1 was cooperative in breast cancer.
Chk2 activates E2F-1 in response to DNA damage.
But there are few systematic reports on mutation of CHK2 in colorectal cancer.
The CHK2 mutation in colorectal cancer is a low frequency event.
The relative contribution of CHK1 and CHK2 to Adriamycin-induced checkpoint.