Ask about this productRelated genes to: CHK1 protein
- Gene:
- CHEK1 NIH gene
- Name:
- checkpoint kinase 1
- Previous symbol:
- -
- Synonyms:
- CHK1
- Chromosome:
- 11q24.2
- Locus Type:
- gene with protein product
- Date approved:
- 1998-04-21
- Date modifiied:
- 2011-11-11
Related products to: CHK1 protein
Related articles to: CHK1 protein
- Metastatic castration-resistant prostate cancer (mCRPC) remains a leading cause of cancer-related mortality in men. Although poly(ADP-ribose) polymerase inhibitors (PARP inhibitor) are approved for mCRPC patients with homologous recombination repair (HRR) deficiencies, clinical trials combining Olaparib with PD-1/PD-L1 inhibitors have shown limited efficacy in unselected populations. To investigate the immunomodulatory effects of PARP inhibitor in an unbiased manner, we performed bulk RNA sequencing on HRR-proficient MycCaP cells treated with the PARP inhibitor (Olaparib) versus vehicle control. Transcriptomics analysis revealed robust upregulation of CD73 (NT5E), an ectoenzyme and emerging immune checkpoint that generates extracellular adenosine, suggesting an adaptive mechanism that undermines Olaparib efficacy and promotes immunosuppression. CD73 induction by Olaparib was validated in both human and mouse prostate cancer cell lines, with more pronounced effects in HRR-compromised PTEN knockout (KO) cells. Mechanistically, olaparib-driven CD73 expression was mediated through DNA damage-activated ATR-CHEK1-IRF1 and TGF-β1-AKT signaling pathways. In parallel, Olaparib enhanced tumor immunogenicity by activating type I interferon (IFN) signaling and antigen presentation machinery. In vivo, combining olaparib with CD73 blockade significantly delayed tumor growth, improved T-cell infiltration, and augmented CD8⁺ T-cell effector function across HRR-proficient and PTEN KO prostate cancer models. These findings identify Olaparib-induced CD73 upregulation as an adaptive resistance mechanism and support Olaparib plus CD73 blockade as a promising therapeutic strategy for advanced prostate cancer, irrespective of HRR status. - Source: PubMed
Publication date: 2026/08/18
Xie PingMa RenqiangZhang MinghuiFan JieTang HuiSong LongzhenWan YongKuzel Timothy MFang DeyuCui WeiguoWu Jennifer DAbdulkadir Sarki AZhang YiPatnaik AkashZhang Bin - Aflatoxin B1 (AFB1) is a potent group 1 carcinogen closely associated with hepatocellular carcinoma (HCC), particularly in regions with high dietary exposure and concurrent hepatitis B virus infection. However, the molecular mechanisms by which AFB1 promotes HCC progression remain incompletely understood, and there is a lack of prognostic models specifically tailored to AFB1-associated HCC. Integrating bioinformatics and network toxicology approaches may help identify key genes and construct reliable predictive tools for this unique subtype of liver cancer. This study aims to identify AFB1-liver cancer key genes and their functional pathways, to establish a prognosis prediction model for AFB1-liver cancer patient, and analyze its performance, and to reveal the binding characteristics between AFB1 and model proteins. - Source: PubMed
Publication date: 2026/06/24
Wang ChunmeiLi JingYuan YumanLiu LiliHe YanLei Bingxi - Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, with limited therapeutic efficacy due to tumor heterogeneity in conventional treatments. In the present study, an integrative, network pharmacology approach was employed to elucidate the multi-target mechanism of action of phytochemicals derived from Glossocardia bosvallia against NSCLC. Among 38 phytocompounds identified, 31 compounds that satisfied pharmacokinetic properties were selected for subsequent analysis. Ligand-based target prediction identified 429 potential protein targets, which are integrated with the top 250 differentially expressed genes obtained from the GSE33532 dataset. Intersection analysis identified eight therapeutic targets: PTGES, SRD5A1, CDK1, KIF11, TOP2A, CDC45, MB, and CHEK1. Protein-protein interaction and enrichment analyses demonstrated that these targets are predominantly involved in cell cycle regulation, mitotic cell cycle, and DNA replication pathways. Gene expression analysis demonstrated significant overexpression of the prioritized targets in NSCLC tissues, while survival analysis identified CHEK1 as the gene significantly associated with survival (p < 0.05). Molecular docking identified TOP2A_quinic acid as the most favorable complex, exhibiting a binding affinity of -12.27 kcal/mol, KIF11_linoleic acid as -12.10 kcal/mol and CHEK1_2,3-dihydro-3,5-dihydroxy-6-methyl-4h-pyran-4-one as -6.75 kcal/mol, which was further validated by dynamic simulations, principal component analysis based free energy landscape, and DSSP analysis, confirming the stability of the protein. This integrative framework provides a robust strategy for identifying biologically relevant and therapeutically actionable targets supporting the potential of G. bosvallia-derived phytochemicals as promising candidates for NSCLC. - Source: PubMed
Publication date: 2026/08/04
Kulandhaivel Soundar RajanStalin AntonyMuthuramalingam PandiyanSivaprakasam BalasubramanianJesudass Joseph Sahayarayan - This study aims to identify biologically relevant genes associated with DNA repair pathways in gastric cancer (GC) by integrating multi-omics analyses with causal inference approaches. - Source: PubMed
Publication date: 2026/07/30
Yang JianhuaQiu ZhengSong WenchaoLiu XingWang JinghuiYang Yinfeng - The essential kinase ataxia telangiectasia and Rad3-related (ATR) monitors the replicative (S) phase of the cell cycle to ensure faithful propagation of genetic material. While much is known about the mechanisms governing ATR activity at replication forks, how its effector checkpoint kinase 1 (CHK1) is regulated to create a localized hub of CHK1 activity at sites of replication remains poorly understood. Here, we report that replication termination factor 2 (RTF2), an essential replisome-associated protein, is necessary for maintaining CHK1 signaling at replication forks. RTF2 interacts with CHK1 and functions alongside the core replicative helicase complex-interacting protein CLASPIN to tether CHK1 to sites of DNA replication, controlling replication rates and preventing premature mitotic entry. These findings uncover how RTF2 and CLASPIN poise CHK1 at replication forks to facilitate its activation by ATR, creating fork-localized CHK1 activity that fuels unperturbed S-phase progression and promotes genome stability by maintaining the intrinsic S-G checkpoint. - Source: PubMed
Publication date: 2026/08/05
Broton CaylaMiller Catherine L WRuiz Penelope DBlobel Nicolas JYao YibingConti Brooke ASchmid Ernst WWalter Johannes CSmogorzewska Agata