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- Table of Contents
Facts about Serine/threonine-protein kinase Chk1.
Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A in'Ser-178' and'Thr-507' and phosphorylation of CDC25C in'Ser-216' creates binding sites for 14-3-3 proteins that inhibit CDC25A and CDC25C.
Human | |
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Gene Name: | CHEK1 |
Uniprot: | O14757 |
Entrez: | 1111 |
Belongs to: |
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protein kinase superfamily |
Checkpoint, S. pombe, homolog of, 1; CHEK1; CHK1 (checkpoint, S.pombe) homolog; CHK1 checkpoint homolog (S. pombe); Chk1; CHK1serine/threonine-protein kinase Chk1; EC 2.7.11; EC 2.7.11.1
Mass (kDA):
54.434 kDA
Human | |
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Location: | 11q24.2 |
Sequence: | 11; NC_000011.10 (125624910..125676256) |
Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon.
Nucleus. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nuclear export is mediated at least in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B.
This article will cover the CHEK1 Marker, its potential in cancer treatment, and its correlation with genotoxicity. This article discusses the Expression Level, Correlation With Genotoxicity, as well as Potential in Cancer Therapy. It is applicable for scientists worldwide. Get the Boster Bio: The Best Uses of CHEK1 Marker eBook to learn more about this unique marker. Learn how to use it in your research.
The CHEK1 genetic marker is a variant of a protein involved mitosis. Multiple myeloma (MM) is characterized by abnormal amplification of the centrosomes. This can lead to more than two centrosomes. These abnormal centrosomes contribute to genomic instability in MM. CEP170 was found in high-throughput MM patient cohorts. This gene plays a crucial role in microtubule structure. CIN is characterized by abnormal microtubule organization. The overexpression of CEP170 in MM cells induced CIN features, and the mutation of Ser1260 abolished the CIN features.
The mChek1 OE RAW264.7 cell-line was used for testing whether the CHEK1 genes interact with NFATc1 and promote osteoclast growth. Using both a convergent and divergent primer, both the mRNAs were detected. CEP170 expression was associated with lower OS in the TT2 cohort. Furthermore, the mRNA of CHEK1 was resistant to RNase R digestion, indicating that the mRNA of this gene was more stable than its linear counterpart.
Chemotherapeutic agents that target CHEK1 genes can also increase the effectiveness and efficacy of chemotherapy drugs. These drugs are associated in MM patients developing increased resistance to chemotherapy drugs. Tumors grow more slowly when CHEK1 is blocked by RNAi. Consequently, drug-resistant MM cells are more resistant to chemotherapy. Further studies are needed in order to understand how CHEK1 interacts with tumor cells and the response to drug treatments.
Claspin activates Chk1. The CKBD motif phosphorylates a conserved threonine/serine in order to activate Chk1. This activity is mediated via a third protein. It could be the Cdc7 kinase or the casein-kinase 1. This gene can be used in many research applications.
CHK1 interacts not only with mitosis but also with many downstream effectors. DNA damage is a common example. Chk1 phosphorylates Cdc25 and degrades it through the proteasome, which is responsible for the cell cycle. Cdc25 phosphorylation, therefore, is one its primary targets.
CHEK1 is a serine/threonine kinase that is an essential component of the G2/M checkpoint. It holds a cell in G2 until it's ready to enter the mitotic stage. This delay gives cells enough time to repair DNA damage or to die if the damage is irreversible. To allow the cell into mitosis during the transition from G2-M phase, Chk1 needs to be inactivated.
Boster bio cells were analyzed using immunoblotting methods to determine p53 status and CHEK1 gene expression. Co-injections of chek1 mRNA along with the cyclin B1 genome showed that p53-deficient cells were more sensitive MK-1775 than those who had been def/-cells. In addition, wee1S44A and p53 protein levels were positively correlated with def-/-cell survival. Similarly, expression levels of the CHEK1 marker were not significantly affected by def-/-mutants.
CHK1 not only inhibits cell proliferation but also causes DNA damage. This is the primary mechanism by which WEE1 inhibitors and CHK1 inhibitors create cytotoxic synergy. Premature mitosis may be the secondary mechanism of action, but it may not affect cell growth inhibition. These results are promising for future cancer treatment. The next question is which drug is more efficient, WEE1 oder CHEK1
FOXM1 is a cell cycle upregulated gene. It is associated with basal-like and TNBC tumors, and HER2+ subtypes were inversely related. The FOXM1 target gene in the ER-positive/PR-/HER2-positive breast cancer subtypes exhibited upregulation of FOXM1 in these tumors. Its counterpart gene, HER2, is human epidermal growth factors receptor 2.
To determine the cyto-genotoxicity of nanoparticles, multiparametric approaches are required. In fibroblasts, AgNPs showed the highest cytotoxicity. CeO2 and TiO2 NPs were found to have transient genotoxicity but no significant toxicity. Correlations between particle size and toxicity have been analyzed in several studies. Table 1 summarizes the results.
Flux cytometry was used to measure genotoxicity, cell uptake, and transmission electron microscopy was used. In addition, the cell-transforming ability was determined using an anchorage-independent soft-agar assay. The results in all cases indicated a significant correlation between genotoxicity and cell-transforming ability. The study also showed that NPs caused cell death inducing mutations of p53 function were less common when p53 function was lost.
Engineered nanoparticles (or ENPs) have many applications in biology, medicine and industry. ENPs (or engineered nanoparticles) can build up in the human body. These nanoparticles can have a wide range of effects on different organs. ENP-based cancer therapies can be improved by understanding the mechanisms that ENPs trigger apoptosis of cancer cells.
Bacteria possess great potential as cancer therapy. These bacteria are capable of colonizing solid tumours and inhibiting their growth. In some cases, colonization may result in tumor clearing and growth retardation. Different bacteria strains are capable of colonizing hypoxic tumors and killing cancer cells. Using this knowledge, researchers are developing a cancer therapy that targets the specific area of the tumor.
These gold nanoparticles could be used as cancer treatments. MD Anderson and Rice University carried out a study to determine if gold nanoshells could improve radiation delivery to cancer cells. Although they are too small and ineffective to penetrate deep into cancerous cells, the small-sized gold nanoparticles can be used to enhance cancer-specific radiation delivery. These findings indicate that these gold nanoparticles are highly effective in treating cancer and are worth further investigation.
The development and use of chimeric cells receptors is another promising way to develop personalized cancer therapies. These antibodies are composed only of single chains of an antigen linked to a signal transforming domain on primary T-cells. The advantage of this approach is that it can bypass defects in antigen presentation. It can also transduce primary and secondary T cells using retroviral vectors. Additionally, chimeric cells can target one of the most common types cancers: the carcinoembryonic algen (CEA).
PMID: 9278511 by Sanchez Y., et al. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25.
PMID: 9382850 by Flaggs G., et al. Atm-dependent interactions of a mammalian chk1 homolog with meiotic chromosomes.