CHEK1 Proteine (CHEK1)

Human Checkpoint Kinase 1 (CHEK1) Interaktionspartner

1. Targeting the ATR/CHK1 axis could result in reversing of drug resistance in small cell lung cancer.

2. Inhibition of checkpoint kinase 1 following gemcitabine-mediated S phase arrest results in CDC7- and CDK2-dependent replication catastrophe.

3. A pulse of gemcitabine and CHK1i followed by WEE1i durably suppressed tumor cell growth.

4. The ATR-Chk1 and ATM-Chk2 signalings in male breast cancer (MBC).

5. control of CHK1 localization between the nucleus and cytoplasm.

6. Studies indicate mechanism for translocation of Tuberous Sclerosis Complex (TSC complex) protein to lysosomes in response to DNA damage, which depends on ATM and Rad3-related protein (ATR)/checkpoint kinase 1 (Chk1)-mediated rhoB GTP-binding protein (RhoB) phosphorylation and sumoylation.

7. These results indicate that, under stressful conditions, maintained mTORC1 signaling in cancer cells promotes survival by suppressing endogenous DNA damage, and may control cell fate through the regulation of CHK1.

8. Chk1 and 14-3-3 proteins cooperate to inactivate the transcriptional repressor functions of atypical E2F proteins. This mechanism might be of particular importance to cancer cells, since they are exposed frequently to DNA-damaging therapeutic reagents.

9. Study provides evidence that expression of CHEK1 protein is high in breast tumors arising in Nigerian women and is associated with aggressive cancer phenotypes and is a prognostic marker.

10. This study reports the crystal structure of the human Chk1 putative kinase-associated 1 (KA1) domain, demonstrating striking structural homology with other sequentially diverse KA1 domains. Separately purified Chk1 kinase and KA1 domains are intimately associated in solution, which results in inhibition of Chk1 kinase activity.

11. The nuclear transcription factor Y subunit beta (NFYB)-E2F transcription factor 1 (E2F1) pathway displays a crucial role in the chemoresistance ofoxaliplatin-resistant colorectal cancer (OR-CRC) by inducing the expression and activation of checkpoint kinase 1 (CHK1), suggesting a possible therapeutic target for oxaliplatin resistance in CRC.

12. Blocking apoptosis alone is insufficient to allow the subsequent outgrowth of primary B cells lacking CHK1 in vivo or B lymphoma lines in vitro, as these cells trigger p53- dependent cell cycle arrest in response to the accumulating DNA damage.

13. Chk1 and Chk2 are significantly expressed in human sperm. In case of sperm DNA damage, up-regulated Chk1 expression may enhance sperm apoptosis and lead to asthenospermia, while increased Chk2 expression may inhibit spermatogenesis and result in oligospermia.

14. CHK1 and CHK2 and their activated forms are frequently expressed in HGSC effusions, with higher expression following exposure to chemotherapy, and their expression is related to survival.

15. expression of AURKA and CHEK1 was linked with detrimental outcome in patients. Our data describe a synthetic lethality interaction between CHEK1 and AURKA inhibitors with potential translation to the clinical setting

16. DNA alkylation damage leads to ATR-Chk1 activation in cancer cells and ATR-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage.

17. Expression levels of phosphorylated cdc25A (p-cdc25A) and phosphorylated Chk1 (p-Chk1), belonging to the ATR pathway, were decreased by treatment with Dclk1 inhibitor LRRK2-IN-1 (LRRK), indicating Dclk1 involvement in the ATR pathway

18. these data demonstrate that prexasertib is a specific inhibitor of CHK1 in neuroblastoma and leads to DNA damage and cell death in preclinical models of this devastating pediatric malignancy.

19. our results identify a novel link between XRRA1 and the ATM/CHK1/2 pathway and suggest that XRRA1 is involved in a DNA damage response that drives radio- and chemoresistance by regulating the ATM/CHK1/2 pathway.

20. results show that HGF was involved in regulating Chk1 phosphorylation, and further demonstrate that AKT activity was responsible for this HGF-induced Chk1 phosphorylation.

Xenopus laevis Checkpoint Kinase 1 (CHEK1) Interaktionspartner

1. Inhibition of Drf1 is the primary mechanism by which Chk1 blocks cell-cycle progression in the early embryo and is an essential function of Chk1 at the blastula-to-gastrula stage of development.

2. The study analyzes the role of Chk1 in the replication program in sperm nuclei replicating in Xenopus egg extracts by a combination of experimental and modelling approaches.

3. ATR-Chk1 DDR pathway appears to be dispensable for the preferential association of REV1 to MMC-damaged chromatin.

4. Results show that Chk1 negatively regulates the Treslin-mediated loading of Cdc45 onto chromatin and thereby serves to antagonize the initiation of replication.

5. The MRN complex, in particular the nuclease activity of Mre11, plays an important role in the activation of Chk1 in response to stalled replication forks.

6. DNA polymerase kappa-dependent DNA synthesis at stalled replication forks is important for CHK1 activation.

7. APE2 associates with Chk1; a serine residue (S86) in the Chk1-binding motif of APE2 is essential for Chk1 phosphorylation, indicating a Claspin-like but distinct role for APE2 in ATR-Chk1 signaling.

8. Data show that the death pathway is independent of ERK but relies on activating Bad phosphorylation through the control of both kinases Cdk1 and JNK.

9. Findings reveal that XH2AX has a specific role in anterior neural formation of Xenopus, which is mediated through phosphorylation of XH2AX at Thr(16) by Chk1.

10. mechanism of Chk1 activation at the DNA replication checkpoint

11. Cdc25A is essential for the Chk1-induced cell cycle arrest and the DNA replication checkpoint in early embryos

12. the Chk1 pathway involves claspin, which functions in checkpoint control [review]

13. ATRIP must associate with ATR in order for ATR to carry out the phosphorylation of Chk1 effectively

14. Cut5 plays a crucial role in the initial amplification step of the ATR-Chk1 signaling pathway at the stalled replication fork.

15. Study shows that although ssDNA is not sufficient for checkpoint activation, the amount of ssDNA adjacent to the primer influences the level of Chk1 phosphorylation.

16. Chk1 is activated at the midblastula transition in Xenopus laevis embryos independently of DNA content and the cyclin E/Cdk2 developmental timer.

Mouse (Murine) Checkpoint Kinase 1 (CHEK1) Interaktionspartner

1. An absence of 53BP1 leads to defective ATR-Chk1-p53 signaling.

2. CHEK1 does not have a direct function in meiotic sex chromosome inactivation (MSCI), an essential event in male meiosis, in which ATR is a key regulator.

3. CHK1 expression levels control the timing of lymphomagenesis

4. During neurogenesis, cortical neurons became protected from S-phase Chk1 pathway activation by the DNA methyltransferase Dnmt1, and underwent cell death after S-phase progression.

5. work reveals that simulated microgravity promotes the apoptotic response through a combined modulation of the Uev1A/TICAM/TRAF/NF-kappaB-regulated apoptosis and the p53/PCNA- and ATM/ATR-Chk1/2-controlled DNA-damage response pathways.

6. Chk1(-/-) MEFs exhibited the absence of double-strand breaks, yet cells showed delayed DNA damage recovery with pan-nuclear immunostaining pattern of Histone H2AX.

7. RAD9 has a prominent role in the ATR-Chk1 pathway that is necessary for successful formation of the damage-sensing complex and DNA damage checkpoint signaling.

8. Acute inactivation of E4F1 in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS production, energy stress, and inhibition of de novo pyrimidine synthesis

9. Altogether, our results classify E4F1 as a master regulator of CHK1 activity that ensures high fidelity of DNA replication, thus safeguarding genome stability.

10. Heterozygous loss of Chk1 in a Wnt-driven background resulted in an increase in DNA damage and apoptosis and accelerated both tumour development and progression.

11. PAR, supplied by PARP1, interacts with Chk1 via a novel PAR-binding regulatory (PbR) motif in Chk1, independent of ATR and its activity

12. ATM (pSer-1981)-Chk1 (pSer-345) cascade might have mediated G2/M cell cycle arrest to allowed time to facilitate sperm-derived DNA damage repair in mouse zygotes fertilized with oxygen-stressed sperm.

13. High level of phospho-Chk1 is associated with skin tumors.

14. Chk1 is essential for the developmental formation of murine epidermal melanocytes but hemizygosity has little permanent developmental consequence in this cell type

15. activated Akt1 in Brca1-deficient cells impairs Chk1 nuclear localization and subsequently disrupts interaction of Chk1 and Rad51 leading to homologous recombination defects.

16. Our results uncover a novel p53-independent function for p21 in protecting cells from the lethal effects of DNA damage followed by Chk1 inhibition

17. The stress kinases p38 and JNK are activated when DNA replication is blocked and their activity allows S/M, but not G 2/M, checkpoint maintenance when Chk1 is inhibited.

18. Chk1 is indispensable for prophase I arrest and functions in G 2/M checkpoint regulation in meiotic oocytes.

19. hypoxia can activate p53 through inactivation of MDMX by the ATR-Chk1-MDMX-14-3-3gamma pathway.

20. complete loss of Chk1 is incompatible with epithelial tumorigenesis, whereas partial loss of function (haploinsufficiency) fosters benign malignant tumor progression.

Cow (Bovine) Checkpoint Kinase 1 (CHEK1) Interaktionspartner

1. The Chk1 directly phosphorylates eNOS Ser(1179) in response to UV irradiation, which is dependent on Hsp90 interaction.