CHEK1 Proteine (CHEK1)

Human Checkpoint Kinase 1 (CHEK1) Interaktionspartner

1. 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.

2. Chk1 and Chk2 (zeige CHEK2 Proteine) 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 (zeige CHEK2 Proteine) expression may inhibit spermatogenesis and result in oligospermia.

3. CHK1 and CHK2 (zeige CHEK2 Proteine) and their activated forms are frequently expressed in HGSC effusions, with higher expression following exposure to chemotherapy, and their expression is related to survival.

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

5. DNA alkylation damage leads to ATR (zeige ANTXR1 Proteine)-Chk1 activation in cancer cells and ATR (zeige ANTXR1 Proteine)-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage.

6. 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

7. these data demonstrate that prexasertib is a specific inhibitor of CHK1 in neuroblastoma (zeige ARHGEF16 Proteine) and leads to DNA damage and cell death in preclinical models of this devastating pediatric malignancy.

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

9. results show that HGF (zeige HGF Proteine) was involved in regulating Chk1 phosphorylation, and further demonstrate that AKT (zeige AKT1 Proteine) activity was responsible for this HGF (zeige HGF Proteine)-induced Chk1 phosphorylation.

10. Chk1 was linked to DNA damage response bypass by suppressing JNK (zeige MAPK8 Proteine) activation following oxidative stress, promoting cell cycle progression despite DNA damage.

Xenopus laevis Checkpoint Kinase 1 (CHEK1) Interaktionspartner

1. Inhibition of Drf1 (zeige DBF4B Proteine) 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 (zeige CDC45 Proteine) onto chromatin and thereby serves to antagonize the initiation of replication.

5. The MRN complex, in particular the nuclease (zeige DCLRE1C Proteine) activity of Mre11 (zeige MRE11A Proteine), plays an important role in the activation of Chk1 in response to stalled replication forks.

6. DNA polymerase kappa (zeige POLK Proteine)-dependent DNA synthesis at stalled replication forks is important for CHK1 activation.

7. APE2 (zeige APEX2 Proteine) associates with Chk1; a serine residue (S86) in the Chk1-binding motif of APE2 (zeige APEX2 Proteine) is essential for Chk1 phosphorylation, indicating a Claspin-like but distinct role for APE2 (zeige APEX2 Proteine) in ATR-Chk1 signaling.

8. Data show that the death pathway is independent of ERK (zeige MAPK1 Proteine) but relies on activating Bad phosphorylation through the control of both kinases Cdk1 (zeige CDK1 Proteine) and JNK (zeige MAPK8 Proteine).

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

10. mechanism of Chk1 activation at the DNA replication checkpoint

Mouse (Murine) Checkpoint Kinase 1 (CHEK1) Interaktionspartner

1. CHK1 expression levels control the timing of lymphomagenesis

2. During neurogenesis, cortical neurons became protected from S-phase Chk1 pathway activation by the DNA methyltransferase (zeige DNMT1 Proteine) Dnmt1 (zeige DNMT1 Proteine), and underwent cell death after S-phase progression.

3. work reveals that simulated microgravity promotes the apoptotic response through a combined modulation of the Uev1A/TICAM/TRAF (zeige TRAF1 Proteine)/NF-kappaB (zeige NFKB1 Proteine)-regulated apoptosis and the p53 (zeige TP53 Proteine)/PCNA (zeige PCNA Proteine)- and ATM (zeige ATM Proteine)/ATR-Chk1/2-controlled DNA-damage response pathways.

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

5. RAD9 (zeige RAD9A Proteine) 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.

6. Acute inactivation of E4F1 (zeige E4F1 Proteine) in these cells results in CHK1-dependent checkpoint deficiency and multiple mitochondrial dysfunctions that lead to increased ROS (zeige ROS1 Proteine) production, energy stress, and inhibition of de novo pyrimidine synthesis

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

8. Heterozygous loss of Chk1 in a Wnt (zeige WNT2 Proteine)-driven background resulted in an increase in DNA damage and apoptosis and accelerated both tumour development and progression.

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

10. ATM (zeige ATM Proteine) (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.

Cow (Bovine) Checkpoint Kinase 1 (CHEK1) Interaktionspartner

1. The Chk1 directly phosphorylates eNOS (zeige NOS3 Proteine) Ser (zeige SIGLEC1 Proteine)(1179) in response to UV irradiation, which is dependent on Hsp90 (zeige HSP90 Proteine) interaction.