Regulation of chk1.
Assessment of chk1 phosphorylation as a pharmacodynamic biomarker of chk1 inhibition.
The position of Chk1 in cancer research.
And it was revealed that Chk1 was ubiquitinated by GA.
CHK1 kinase activity assay.
AZD7762 inhibited Chk1 autophosphorylation (S296 Chk1), stabilized Cdc25A, and increased ATR/ATM-mediated Chk1 phosphorylation (S345 Chk1).
Regulatory motifs in Chk1.
CHK1 kinase activity assay.
Unleashing Chk1 in cancer therapy.
Chk1 suppressed cell death.
New partners for Chk1.
LY2603618 inhibited Chk1 autophosphorylation (S296 Chk1) and increased DNA damage-mediated Chk1 phosphorylation (S345 Chk1).
Cytoplasmic occurrence of the Chk1/Cdc25 pathway and regulation of Chk1 in Xenopus oocytes.
Cdc25 associated with Chk1 in vivo and was phosphorylated when copurified in Chk1 complexes.
The interaction between CK2beta and Chk1 leads to an increase in the Cdc25C phosphorylation activity of Chk1.
Wild-type Chk1 could rescue all the defects of Chk1-null cells.
Claspin is phosphorylated in the Chk1-binding domain by a kinase distinct from Chk1.
Plk2 was demonstrated to interact with Chk2, Chk1, Serine 317-phosphorylated Chk1 and p53.
Phosphorylation of Chk1 by ATR is antagonized by a Chk1-regulated protein phosphatase 2A circuit.
Importantly, dephosphorylation of Chk1 by PP2A is regulated, in part, by the kinase activity of Chk1.
Treatment with a Chk1 inhibitor and silencing of Chk1 also reduced the frequency in HCT116 mutants.
chk1(-) cells were sensitive to cisplatin and Chk1 was phosphorylated in response to cisplatin treatment.
Treatment of cells with CHK1 inhibitors increased the phosphorylation of CHK1 and ERK1/2.
Metnase decreases Chk1 interaction with DDB1, and decreases Chk1 ubiquitination.
Cdk phosphorylation of Chk1 regulates efficient Chk1 activation and multiple checkpoint proficiency.
Inhibition of Mcph1 expression led to downregulation of Chk1 and reduction of Chk1 kinase activity.
These phosphorylations promote binding of Chk1 to Claspin and ensuing activation of Chk1 by ATR.
Chk1 activation and the nuclear/cytoplasmic ratio.
Chk1 is phosphorylated in response to DNA damage.
Inhibition of Chk1 by activated PKB/Akt.
Chk1 is required to maintain claspin stability.
Chk1 inhibitors for novel cancer treatment.
Chk1 is required for spindle checkpoint function.
They are not active against the related Chk1 kinase.
Expanded roles for Chk1 in genome maintenance.
Chk1 and Claspin potentiate PCNA ubiquitination.
In addition, menin and Chk1 interact in vivo.
Enhancing CHK1 inhibitor lethality in glioblastoma.
Targeting Chk1 in the replicative stress response.
Methods for studying checkpoint kinases - Chk1.
Chk1 is the major mediator of this phosphorylation event.
Novel insights into Chk1 regulation by phosphorylation.
Checkmate to CHK1 in T-cell ALL?
The findings of decreased Chk1 activity and accumulation of Cdc25A, a protein targeted for degradation by Chk1, confirmed that Chk1 function was impaired.
Furthermore, both chk1 mutants survive to Camptothecin treatment despite undetectable Chk1-1 or Chk1-2 phosphorylated forms.
Dis2 abrogates Chk1 phosphorylation and activation in vivo, and dephosphorylates Chk1 and a phospho-S345 Chk1 peptide in vitro.
Radiation-induced centrosome amplification was abrogated in Chk1(-/-) DT40 cells, but occurred at normal levels in Chk1(-/-) cells transgenically expressing Chk1.
This review discusses the rationale of Chk1 as an anticancer target, the structural basis for designing Chk1 inhibitors, and recently disclosed Chk1 inhibitors.
MEPE/OF45, interacting with CHK1, increases CHK1 half-life and decreases CHK1 degradation through the ubiquitine-mediated pathway.
Ser296 phosphorylation is catalysed by Chk1 itself after Chk1 phosphorylation by ATR, and then ATR sites are rapidly dephosphorylated on Ser296-phosphorylated Chk1.
The association of Chk1 with meiotic chromosomes and levels of Chk1 protein depend upon a functional Atm gene product, but Chk1 is not dependent upon p53 for meiosis I functions.
When coexpressed in oocytes or embryos, the AIR can interact with and inhibit the kinase domain of Chk1, but not full-length Chk1, suggesting an autoinhibitory intramolecular interaction in the ...
Chk1 activation seems to need two steps of interaction changes: the loss of Rad3-Chk1 and Rad3-Crb2 interactions, and the association between hyperphosphorylated forms of Chk1 and Crb2.
The ATR pathway was further investigated by transiently transfecting HEK293 cells with two mammalian CHK1 expression constructs--full length CHK1 and truncated active CHK1.
Although Chk1 dissociates from the chromatin upon UV damage, no change in the mobility of GFP-Chk1 was observed, supporting the notion that Chk1 is a highly dynamic protein.
CHK1 inhibition by AZD7762 preferentially sensitizes high CHK1 expressing cells, H1299, to anti-metabolite chemotherapy as compared with low CHK1 expressing H1993 cells.
These data define a novel pathway for Chk1 regulation, whereby a target of Chk1, Metnase, feeds back to amplify Chk1 stability, and therefore enhance replication fork arrest.
Activation of Chk1 kinase also requires its association with Claspin, an adaptor protein essential for Chk1 protein stability, recruitment and ATR-dependent Chk1 phosphorylation.
siRNA targeting Chk1 abrogated approximately 55% of Chk1 expression and also promoted apoptosis, suggesting that Chk1 plays anti-apoptotic roles in response to US.
iPOND studies reveal that Chk1 associates readily with the unperturbed replication fork and that PAR is required for efficient retention of Chk1 and phosphorylated Chk1 at the fork.
Replication checkpoint enforced by kinases Cds1 and Chk1.
These responses were associated with phosphorylation of the checkpoint kinase Chk1.
Tissue-specific regulation of Chk1 expression by p53.
However, the function of Chk1 in mammals has remained unknown.
The kinase domain of Chk1 gene is absent in this isoform.
The protein kinase Chk1 enforces the DNA damage checkpoint.
Activation of Xenopus Chk1 by mutagenesis of threonine-377.
Lethal errors in checkpoint control--life without Chk1.
Thus, Chk1 inhibitor is not expected to enhance the toxicity of paclitaxel.
A novel mechanism of checkpoint abrogation conferred by Chk1 downregulation.
Cells defective in CHK1 are sensitive to ionizing radiation (IR).
BRCA1 and Claspin then function to activate the tumor suppressor Chk1.
CHK1 affects cell sensitivity to microtubule-targeted drugs.
The ATR and Chk1 kinases are essential to maintain genomic integrity.
Chk1 and Chk2 kinases in checkpoint control and cancer.
Regulation of Chk1 kinase by autoinhibition and ATR-mediated phosphorylation.
Rad3 activates the effector protein kinase Chk1 by phosphorylation.