Active CHK1
- Known as:
- Active CHK1
- Catalog number:
- 7735-100
- Product Quantity:
- 100 ug
- Category:
- -
- Supplier:
- Biovis
- Gene target:
- Active CHK1
Related genes to: Active CHK1
- 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: Active CHK1
Related articles to: Active CHK1
- 1,2-Unsaturated pyrrolizidine alkaloids (PA) induce severe acute and chronic hepatotoxicity. Effects include an impairment of the cell cycle. To elucidate this effect, cell cycle progression was analyzed by flow cytometry, changes in cell and nucleus size, differential gene expression and protein phosphorylation patterns of regulatory key proteins in the Chinese hamster lung fibroblast cell line V79 and/or the human hepatoblastoma cell line HepG2, both overexpressing human CYP3A4 (V79/HepG2). Lasiocarpine, a potent PA representative, reduced the cell viability of human CYP3A4-overexpressing cell lines concentration-dependently. Microscopic observation showed a marked increase in cell and nucleus size of V79 cells after exposure to 10 µM lasiocarpine. In the human CYP3A4-overexpressing cell lines, cells accumulate in G/M phase after lasiocarpine treatment. Based on these findings, the gene expression pattern of cell cycle-related genes was investigated in HepG2 cells showing a decrease of e. g. WEE1, and CHEK1 and an increase of PAK1 and ATM. While results on cell cycle regulation at the level of gene expression are of limited relevance, protein phosphorylation plays an important role. Therefore, we also elucidated the protein phosphorylation status of regulatory key proteins. The results clearly indicate an induction of the DNA damage response and a late G2 arrest. In conclusion, an impairment of the cell cycle was observed. It correlates with the metabolic activation of lasiocarpine and is most likely mediated by adduct formation of the reactive pyrrole esters with DNA, leading to a disruption of cellular homeostasis and genomic instability. - Source: PubMed
Publication date: 2025/09/16
Hessel-Pras StefanieBeckschulte MarlenaPeters AntoniaKoellner AnjaRosskopp BeatriceStahl AaronTemplin MarkusSprenger HeikeBoehmert LindaKuepper Jan-HeinerSachse BenjaminSchaefer Bernd - Skin cancer remains a significant global health challenge, with rising incidence and associated mortality in late-stage and drug-resistant cases. This underscores a continuing need for more effective novel therapeutic options that can be utilized for efficient management of skin cancers. A promising approach involves exploiting novel targets, which are dysregulated in skin cancer, either alone or in combination with existing therapeutics. Among these, polo-like kinases (PLKs), a family of serine/threonine kinases, has emerged as promising candidates due to their essential role in cell cycle and maintaining genomic stability, key hallmarks of cancer. Within this family, polo-like kinase 4 (PLK4) stands out as a structurally distinct member and the master regulator of centriole duplication, ensuring this process occurs only once per cell division. Dysregulation of PLK4 can disrupt genomic integrity, contributing to tumorigenesis, thus making it a promising target for cancer management. Notably, PLK4 is frequently overexpressed in several cancers, including skin cancer, and its precise role in skin cancer is an area of current investigation. Further, several small-molecule PLK4 inhibitors such as centrinone, YLZ-F5, CFI-400945, and RP-1664 have demonstrated efficacy in targeting PLK4. Among these, CFI-400945 has advanced to clinical trials, where it has shown modest anti-cancer activity. In this review, we provide a comprehensive overview of the known functions of PLK4 in skin cancer. Additionally, we discuss potential mechanistic insights into PLK4's involvement in skin cancer progression by extrapolating evidence from studies in other cancer types including colorectal cancer, thyroid cancer, lymphomas, leukemia, etc., while identifying gaps for future research. - Source: PubMed
Publication date: 2025/09/04
Jaiswal TanyaMuntaqua DurdanaAhmad Nihal - Microscopic examination of biopsy tissues remains essential for cancer diagnosis, despite advancements in sequencing technologies. Alterations in nuclear size or the nuclear-to-cytoplasmic ratio are hallmark features of cancer cells and often correlate with disease progression. However, the mechanisms underlying nuclear size abnormalities and their impact on tumor progression remain unclear. In this study, we demonstrate that nuclear hypertrophy occurs in response to enhanced DNA replication stress, a key characteristic of cancer cells. Increased actin polymerization within the nucleus appears to be the primary mechanism driving nuclear hypertrophy downstream of the ATR-CHEK1 pathway. Replication stress-induced nuclear hypertrophy alters transcriptomic profiles and chromatin topology, while reducing the migratory and metastatic capacity of cancer cells. In addition, nuclear hypertrophy in cancer cells is associated with increased infiltration of antitumor immune cells. Our findings suggest that cell-autonomous effects of nuclear hypertrophy do not promote cellular fitness or aggressive characteristics in cancer cells. This may explain why cells with nuclear hypertrophy are not positively selected and persist as a subpopulation during tumor progression and metastasis. Furthermore, the link between replication stress and nuclear hypertrophy provides insights into why enlarged nuclei are consistently observed in advanced-stage cancers. - Source: PubMed
Publication date: 2025/09/10
Kim ChanggonHong SemyeongMa Soo HyeonLee JoochanSo HeeKim Jun YoungShin EunbieLee KippeumChoi SoheePark JuyeonPark YongKeunKim You-MeKim Ji HunKim Joon - Embryonic stem cells (ESCs), which are susceptible to DNA damage, depend on a robust and highly efficient DNA damage response (DDR) mechanism for their survival. However, the implications of physical force-mediated DNA damage on ESC fate remain unclear. We show that stiffness-dependent spreading of mouse ESCs (mESCs) induces DNA damage through nuclear compression, with DNA damage causing differentiation through Lamin A/C. Interestingly, differentiation is associated with DNA damage and activation of the DDR factors such as ATR and CHK1. While ATR is typically known to play roles in DDR pathway, its role during stiffness-mediated nuclear compression and mESC differentiation is unknown. While our results show activation of CHK1 pathway and nuclear enrichment of activated ATR on stiff substrates, inhibiting ATR and CHK1 both result in reduction of Lamin A/C expression by different mechanisms. Overall, we demonstrate that mESC differentiation is driven by nuclear compression-mediated DNA damage and involves ATR-dependent modulation of Lamin A/C. - Source: PubMed
Roy TanusriGhosh SwetlanaPiplani NiyatiSthanam Lakshmi KavithaTiwary NiharikaDhar SayakKonyak W Chingmei WangsaPanigrahi Santosh SurendraSingh PriyaSowpati Divya TejNair SreelajaKumar SushilShekar P ChandraSen Shamik - leaves (FSL), a traditional Chinese ethnomedicinal herbal material used to prepare health-promoting infusions and pharmacologically noted for their robust anti-inflammatory, antioxidant, and broad-spectrum antiviral activities, nevertheless have an as-yet-uncharacterized molecular mechanism of action against human adenovirus (HAdV). - Source: PubMed
Publication date: 2025/08/21
Wang LinglingRen ShuanshanMa XingmingLi YanliuZheng YongyongLi LingCao Luhong