C57BL/6JCya-Cdk18em1/Cya
Common Name:
Cdk18-KO
Product ID:
S-KO-17432
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
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Basic Information
Strain Name
Cdk18-KO
Strain ID
KOCMP-18557-Cdk18-B6J-VB
Gene Name
Product ID
S-KO-17432
Gene Alias
Ctk18; Pctk3
Background
C57BL/6JCya
NCBI ID
Modification
Conventional knockout
Chromosome
1
Phenotype
Document
Application
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Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Cdk18em1/Cya mice (Catalog S-KO-17432) were purchased from Cyagen.”
Strain Description
Ensembl Number
ENSMUST00000027697
NCBI RefSeq
NM_008795
Target Region
Exon 9~15
Size of Effective Region
~2.9 kb
Detailed Document
Overview of Gene Research
Cdk18, also known as PCTK3, is a cyclin-dependent kinase. It belongs to the PCTAIRE subfamily of CDKs, characterized by a serine-to-cysteine mutation in the consensus PSTAIRE motif. After activation by cyclin A2 or phosphorylation at Ser12 by PKA, it can modulate cargo transport in membrane traffic, regulate p53-responsive genes, and maintain genome integrity [1]. It is involved in pathways related to cell cycle checkpoints and DNA repair mechanisms to ensure genome stability [2].
Depletion of Cdk18 in cells causes an increase in endogenous DNA damage and chromosomal abnormalities. Cdk18-depleted cells accumulate in early S-phase, with retarded replication fork kinetics and reduced ATR kinase signaling in response to replication stress [2]. In breast cancer, high Cdk18 protein expression is associated with a triple-negative and basal-like phenotype, as well as improved patient survival, especially in ER-negative breast cancers and those treated with chemotherapy. Also, cells with high levels of endogenous Cdk18 are more sensitive to replication-stress-inducing chemotherapeutic agents [4]. In glioblastoma, MYC-mediated transcriptional repression of Cdk18 generates sensitivity to PARP inhibitors. Cdk18 facilitates ATR activation and homologous recombination, conferring PARP inhibitor resistance [3].
In conclusion, Cdk18 is crucial for maintaining genome stability, especially in relation to replication stress signaling. Its role in diseases such as breast cancer, glioblastoma, and potentially in early ischaemic stroke in sickle-cell-disease patients, as indicated by genetic association studies [5], highlights its importance. Functional studies, especially those using loss-of-function models, have been key in revealing these aspects of Cdk18's biological functions.
References:
1. de Oliveira Pepino, Rebeka, Coelho, Fernanda, Janku, Tatiane Aparecida Buzanello, de Azevedo, Walter Figueira, Canduri, Fernanda. . Overview of PCTK3/CDK18: A Cyclin-Dependent Kinase Involved in Specific Functions in Post-Mitotic Cells. In Current medicinal chemistry, 28, 6846-6865. doi:10.2174/0929867328666210329122147. https://pubmed.ncbi.nlm.nih.gov/33781185/
2. Barone, Giancarlo, Staples, Christopher J, Ganesh, Anil, Eyers, Patrick A, Collis, Spencer J. 2016. Human CDK18 promotes replication stress signaling and genome stability. In Nucleic acids research, 44, 8772-8785. doi:. https://pubmed.ncbi.nlm.nih.gov/27382066/
3. Ning, Jian-Fang, Stanciu, Monica, Humphrey, Melissa R, Wakimoto, Hiroaki, Rabkin, Samuel D. 2019. Myc targeted CDK18 promotes ATR and homologous recombination to mediate PARP inhibitor resistance in glioblastoma. In Nature communications, 10, 2910. doi:10.1038/s41467-019-10993-5. https://pubmed.ncbi.nlm.nih.gov/31266951/
4. Barone, Giancarlo, Arora, Arvind, Ganesh, Anil, Madhusudan, Srinivasan, Collis, Spencer J. 2018. The relationship of CDK18 expression in breast cancer to clinicopathological parameters and therapeutic response. In Oncotarget, 9, 29508-29524. doi:10.18632/oncotarget.25686. https://pubmed.ncbi.nlm.nih.gov/30034634/
5. Earley, Eric Jay, Kelly, Shannon, Fang, Fang, Dinardo, Carla, Page, Grier P. 2023. Genome-wide association study of early ischaemic stroke risk in Brazilian individuals with sickle cell disease implicates ADAMTS2 and CDK18 and uncovers novel loci. In British journal of haematology, 201, 343-352. doi:10.1111/bjh.18637. https://pubmed.ncbi.nlm.nih.gov/36602125/
Quality Control Standard
Sperm Test
Pre-cryopreservation: Measurement of sperm concentration, determination of sperm viability.
Post-cryopreservation: A vial of cryopreserved sperms is selected for in-vitro fertilization from each batch.
Environmental Standards:SPF
Available Region:Global
Source:Cyagen