C57BL/6JCya-Cdk18em1flox/Cya
Common Name:
Cdk18-flox
Product ID:
S-CKO-04196
Background:
C57BL/6JCya
Product Type
Age
Genotype
Sex
Quantity
Price:
Contact for Pricing
Basic Information
Strain Name
Cdk18-flox
Strain ID
CKOCMP-18557-Cdk18-B6J-VA
Gene Name
Product ID
S-CKO-04196
Gene Alias
Ctk18; Pctk3
Background
C57BL/6JCya
NCBI ID
Modification
Conditional knockout
Chromosome
1
Phenotype
Document
Application
--
Note: When using this mouse strain in a publication, please cite “C57BL/6JCya-Cdk18em1flox/Cya mice (Catalog S-CKO-04196) 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 member of the cyclin-dependent kinase (CDK) family. Its catalytic activity requires a cyclin regulatory subunit. Cdk18 is involved in several important biological functions such as modulating cargo transport in membrane traffic, being a p53-responsive gene, and regulating genome integrity. It is also associated with pathways like the regulation of replication stress signaling and the FAK/Rho signaling pathway [1,2,4].
Depletion of Cdk18 in cells causes an increase in endogenous DNA damage, chromosomal abnormalities, and cells accumulate in early S-phase with retarded replication fork kinetics and reduced ATR kinase signaling in response to replication stress. Mechanistically, it interacts with RAD9, RAD17 and TOPBP1, and its deficiency leads to a decrease in RAD17 and RAD9 chromatin retention during 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, and cells with high endogenous Cdk18 expression show increased sensitivity to replication-stress-inducing chemotherapeutic agents [5]. In glioblastoma, MYC-mediated transcriptional repression of Cdk18 generates sensitivity to PARP inhibitors, and Cdk18 promotes ATR activation and homologous recombination to mediate PARP inhibitor resistance [3].
In conclusion, Cdk18 plays a crucial role in maintaining genome stability, especially in regulating replication stress signaling. Its dysregulation is related to various diseases such as cancer, cerebral ischemia, and metabolic diseases. Studies using cell-based loss-of-function experiments and analysis of its expression in human cancer tissues have provided insights into its functions in disease conditions, highlighting its potential as a target for drug design.
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. Matsuda, Shinya, Kawamoto, Kohei, Miyamoto, Kenji, Tsuji, Akihiko, Yuasa, Keizo. 2017. PCTK3/CDK18 regulates cell migration and adhesion by negatively modulating FAK activity. In Scientific reports, 7, 45545. doi:10.1038/srep45545. https://pubmed.ncbi.nlm.nih.gov/28361970/
5. 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/
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