CKS2 (CDC28 protein kinase regulatory subunit 2)
2010-02-01 Yongyou Zhang AffiliationCase Western Reserve University, WRB-3101, 2103 Cornell Rd, Cleveland, OH 44106, USA
DNA/RNA
Genomic organization of the CKS2 gene.
Description
Three exons, spans approximately 5.5 kb of genomic DNA in the centromere-to-telomere orientation. The translation initiation codon ATG is located in exon 1, and the stop codon in exon 3.
Transcription
mRNA is 627 bp.
Pseudogene
1 processed, non-expressed, pseudogene in human genome.
Proteins
Note
The Cks2 protein can form a special homohexamer structure. Six kinase subunits can bind the assembled hexamer, and therefore this Cks2 hexamer may participate in cell cycle control by acting as the hub for Cdk multimerization in vivo.
Description
The open reading frame encodes a 79 amino acid protein, with an estimated molecular weight of approximately 9860 Da.
Expression
Basic level expression in all mammalian cells and aberrant expression in cancer cells.
Localisation
Cytoplasm and nucleus.
Function
CKS2 protein binds to the catalytic subunit of the cyclin-dependent kinases and is essential for their biological function of cell cycle control. Especially, CKS2 is required for the first metaphase/anaphase transition of mammalian meiosis. The mice ablated of Cks2 are viable but sterile in both sexes. Sterility is due to failure of both male and female germ cells to progress from the first meiotic metaphase to anaphase. In cancer cells, CKS2 may protect the cells from apoptosis.
Homology
The CKS2 protein is evolutionary conserved. Mammalian cells express two well-conserved CKS members, like the human CKS2 and CKS1B proteins. CKS2 and CKS1B may have redundant function in some context and have different functions in other context. The CKS2 protein is highly conserved cross species.
Mutations
Note
Mutation of glutamine for glutamate 63 (E63Q), disrupted the essential biological function of the protein and significantly reduced its ability to bind to cyclin-dependent kinases, but preserves protein structure and assembly.
Implicated in
Entity name
Various cancers
Note
Emerging evidence showed that the expression of CKS2 is elevated in multiple cancers, including prostate cancer, breast cancer, gastric cancer, colorectal cancer, uterine cervical cancer, bladder cancer, nasopharyngeal carcinoma, melanoma, lymphoma, lung cancer, esophageal squamous cell carcinoma et al. The expression of CKS2 is correlated with poor survival rate of the patients of some cancers.
Prognosis
Overexpression of CKS2 has been reported to be associated with high aggressiveness and a poor prognosis in multiple cancers, including breast cancer, prostate cancer, colon cancer, hepatocellular carcinoma and meningiomas et al.
Entity name
Hepatocellular carcinoma (HCC)
Note
Expressions of CKS2 were significantly higher in HCC compared with the adjacent noncancerous tissues (including chronic hepatitis and cirrhosis) and normal liver tissues. Overexpression of CKS2 in HCC were closely associated with poor differentiation features (Shen et al., 2010).
Entity name
Gastric cancer
Note
CKS2 was showed to be significantly unregulated in gastric cancers. The high level of CKS2 was highly correlated with tumor differentiation and pathological grade of the tumor size, lymph node, and metastasis stage (Kang et al., 2009).
Entity name
Prostate cancer
Note
CKS2 were significantly unregulated in prostate tumors of human and animal models, as well as prostatic cancer cell lines. Forced expression of CKS2 in benign prostate tumor epithelial cells promoted cell population growth. Inhibition of CKS2 expression can induce programmed cell death and inhibit the tumorigenesis. (Lan et al., 2008). Over expression of CKS2 may linked with androgen-independent prostate cancer progression (Stanbrough et al., 2006).
Entity name
Colon cancer
Note
CKS2 was reported significantly overexpressed in microdissected invasive colon tumor cells compared with adjacent normal epithelial cells (Wiese et al., 2007). CKS2 was also showed to be higher in liver metastasis compared with primary colon cancer (Lin et al., 2007).
Oncogenesis
Amplification and overexpression of CKS2 were associated with liver metastasis and poor prognosis in colon cancer. CKS2 is required for germ cell to go past the first meiotic metaphase and enter anaphase. In cancer cell, overexpression of CKS2 can accelerate the cell cycles and promote the cell proliferation. Recently research showed that CKS2 may also be involved in apoptosis and metabolism since it can protect mitochondrial genome integrity via interaction with mitochondrial single-stranded DNA-binding protein. Study also showed CKS2 as a transcriptional target downregulated by the tumor suppressor p53. CKS2 expression was found to be repressed by p53 both at the mRNA and the protein levels, which may provide a mechanism that explain why CKS2 is upregulated in many types of cancer. All of these suggest that CKS2 alterations may have a significant biological role in the tumorigenesis in different tissue. The novel therapeutic strategy for cancer though may be developed via inhibiting the CKS2 activity. Therefore, disruption of CKS2-Cyclin Complex assembly or down-regulation of CKS2 expression may be used for cancer therapy.
Entity name
Esophageal squamous cell carcinoma
Note
Gene expression profiling of lymph node metastasis by oligomicroarray analysis and Real-time RT-PCR confirmed that CKS2 is unregulated in laser microdissection of esophageal squamous cell carcinoma compared with adjacent normal tissue (Uchikado et al., 2006).
Entity name
Uterine cervical cancer
Note
CKS2 was showed significantly higher in node positive tumor compared with negative one. The CKS2 expression is correlated with metastatic phenotypes and progression free survival. (Lyng et al., 2006).
Entity name
Bladder cancer
Note
Large-scale gene expression profiling and Real-Time RT-PCR confirmed that a the CKS2 expression is elevated in invasive bladder cancer compared with superficial cancer (Kawakami et al., 2006).
Entity name
Glioblastoma
Note
CKS2 was significantly up-regulated in primary glioblastomas compared with the non-neoplastic brain tissues (Scrideli et al., 2008).
Entity name
Meningioma
Note
This microarray-based expression profiling study showed CKS2 is unregulated in atypical and anaplastic meningiomas compared with benign meningiomas (Fevre-Montange et al., 2009).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16116475 | 2006 | Identification of RASSF1A modulated genes in nasopharyngeal carcinoma. | Chow LS et al |
| 8697818 | 1996 | Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22. | Demetrick DJ et al |
| 12851469 | 2003 | Germline exclusion of Cks1 in the mouse reveals a metaphase I role for Cks proteins in male and female meiosis. | Donovan PJ et al |
| 9632748 | 1998 | Cyclin-stimulated binding of Cks proteins to cyclin-dependent kinases. | Egan EA et al |
| 19885562 | 2009 | Microarray gene expression profiling in meningiomas: differential expression according to grade or histopathological subtype. | Fèvre-Montange M et al |
| 18005268 | 2008 | Myeloma cell expression of 10 candidate genes for osteolytic bone disease. Only overexpression of DKK1 correlates with clinical bone involvement at diagnosis. | Haaber J et al |
| 19034516 | 2009 | Upregulation of the cycline kinase subunit CKS2 increases cell proliferation rate in gastric cancer. | Kang MA et al |
| 16865252 | 2006 | Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling. | Kawakami K et al |
| 18498131 | 2008 | Aberrant expression of Cks1 and Cks2 contributes to prostate tumorigenesis by promoting proliferation and inhibiting programmed cell death. | Lan Y et al |
| 14719106 | 2004 | Genes associated with liver metastasis of colon cancer, identified by genome-wide cDNA microarray. | Li M et al |
| 17428314 | 2007 | Inhibitory effects of estrogen receptor beta on specific hormone-responsive gene expression and association with disease outcome in primary breast cancer. | Lin CY et al |
| 17487416 | 2007 | Genome wide expression profiling identifies genes associated with colorectal liver metastasis. | Lin HM et al |
| 12695690 | 2003 | PC-SPES inhibits cell proliferation by modulating p21, cyclins D, E and B and multiple cell cycle-related genes in prostate cancer cells. | Lu X et al |
| 17054779 | 2006 | Gene expressions and copy numbers associated with metastatic phenotypes of uterine cervical cancer. | Lyng H et al |
| 18625720 | 2008 | Cyclin-dependent kinase-associated proteins Cks1 and Cks2 are essential during early embryogenesis and for cell cycle progression in somatic cells. | Martinsson-Ahlzén HS et al |
| 19837160 | 2010 | Clinical, pathological, proliferative and molecular responses associated with neoadjuvant aromatase inhibitor treatment in breast cancer. | Miller WR et al |
| 8211159 | 1993 | Human CksHs2 atomic structure: a role for its hexameric assembly in cell cycle control. | Parge HE et al |
| 8939596 | 1996 | Cell cycle: reaching for a role for the Cks proteins. | Pines J et al |
| 19786724 | 2010 | CKS proteins protect mitochondrial genome integrity by interacting with mitochondrial single-stranded DNA-binding protein. | Radulovic M et al |
| 17336302 | 2007 | Gene expression of cyclin-dependent kinase subunit Cks2 is repressed by the tumor suppressor p53 but not by the related proteins p63 or p73. | Rother K et al |
| 18398573 | 2008 | Gene expression profile analysis of primary glioblastomas and non-neoplastic brain tissue: identification of potential target genes by oligonucleotide microarray and real-time quantitative PCR. | Scrideli CA et al |
| 12473461 | 2003 | Weak cooperativity in the core causes a switch in folding mechanism between two proteins of the cks family. | Seeliger MA et al |
| 19845855 | 2010 | Clinical significance and expression of cyclin kinase subunits 1 and 2 in hepatocellular carcinoma. | Shen DY et al |
| 12714746 | 2003 | Requirement of Cks2 for the first metaphase/anaphase transition of mammalian meiosis. | Spruck CH et al |
| 16510604 | 2006 | Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. | Stanbrough M et al |
| 17088971 | 2006 | Gene expression profiling of lymph node metastasis by oligomicroarray analysis using laser microdissection in esophageal squamous cell carcinoma. | Uchikado Y et al |
| 10360827 | 1999 | ckshs expression is linked to cell proliferation in normal and malignant human lymphoid cells. | Urbanowicz-Kachnowicz I et al |
| 19175833 | 2009 | Cross-species hybridization of woodchuck hepatitis viral infection-induced woodchuck hepatocellular carcinoma using human, rat and mouse oligonucleotide microarrays. | Wang F et al |
| 8800213 | 1996 | A mutation in the human cyclin-dependent kinase interacting protein, CksHs2, interferes with cyclin-dependent kinase binding and biological function, but preserves protein structure and assembly. | Watson MH et al |
| 17936523 | 2007 | Identification of gene signatures for invasive colorectal tumor cells. | Wiese AH et al |
| 16353136 | 2006 | Genome-wide gene expression profiling of cervical cancer in Hong Kong women by oligonucleotide microarray. | Wong YF et al |
| 15900300 | 2005 | Analysis of differential gene expression in human melanocytic tumour lesions by custom made oligonucleotide arrays. | de Wit NJ et al |
Other Information
Locus ID:
NCBI: 1164
MIM: 116901
HGNC: 2000
Ensembl: ENSG00000123975
Variants:
dbSNP: 1164
ClinVar: 1164
TCGA: ENSG00000123975
COSMIC: CKS2
RNA/Proteins
| Gene ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000123975 | ENST00000314355 | P33552 |
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Small cell lung cancer | KEGG | ko05222 |
| Pathways in cancer | KEGG | hsa05200 |
| Small cell lung cancer | KEGG | hsa05222 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38296306 | 2024 | Prognostic significance of cyclin-dependent kinase subunit 2 (CKS2) in malignant tumours: a meta-analysis and bioinformatic analysis. | 0 |
| 38296306 | 2024 | Prognostic significance of cyclin-dependent kinase subunit 2 (CKS2) in malignant tumours: a meta-analysis and bioinformatic analysis. | 0 |
| 36284444 | 2023 | Cyclin-dependent kinase subunit2 (CKS2) promotes malignant phenotypes and epithelial-mesenchymal transition-like process in glioma by activating TGFβ/SMAD signaling. | 6 |
| 36284444 | 2023 | Cyclin-dependent kinase subunit2 (CKS2) promotes malignant phenotypes and epithelial-mesenchymal transition-like process in glioma by activating TGFβ/SMAD signaling. | 6 |
| 35663965 | 2022 | High Expression of CKS2 Predicts Adverse Outcomes: A Potential Therapeutic Target for Glioma. | 8 |
| 35703112 | 2022 | Prognostic significance of CKS2 and CD47 expression in patients with gastric cancer who underwent radical gastrectomy. | 1 |
| 35899496 | 2022 | Errate: Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis. | 0 |
| 35903032 | 2022 | Knockdown of replication protein A 3 induces protective autophagy and enhances cisplatin sensitivity in lung adenocarcinoma by inhibiting AKT/mTOR signaling via binding to cyclin-dependent kinases regulatory subunit 2. | 1 |
| 36010686 | 2022 | Cyclin-Dependent Kinase Subunit 2 (CKS2) as a Prognostic Marker for Stages I-III Invasive Non-Mucinous Lung Adenocarcinoma and Its Role in Affecting Drug Sensitivity. | 2 |
| 35663965 | 2022 | High Expression of CKS2 Predicts Adverse Outcomes: A Potential Therapeutic Target for Glioma. | 8 |
| 35703112 | 2022 | Prognostic significance of CKS2 and CD47 expression in patients with gastric cancer who underwent radical gastrectomy. | 1 |
| 35899496 | 2022 | Errate: Identification of NDRG Family Member 4 (NDRG4) and CDC28 Protein Kinase Regulatory Subunit 2 (CKS2) as Key Prognostic Genes in Adrenocortical Carcinoma by Transcriptomic Analysis. | 0 |
| 35903032 | 2022 | Knockdown of replication protein A 3 induces protective autophagy and enhances cisplatin sensitivity in lung adenocarcinoma by inhibiting AKT/mTOR signaling via binding to cyclin-dependent kinases regulatory subunit 2. | 1 |
| 36010686 | 2022 | Cyclin-Dependent Kinase Subunit 2 (CKS2) as a Prognostic Marker for Stages I-III Invasive Non-Mucinous Lung Adenocarcinoma and Its Role in Affecting Drug Sensitivity. | 2 |
| 33107644 | 2021 | CKS2 modulates cell-cycle progression of tongue squamous cell carcinoma cells partly via modulating the cellular distribution of DUTPase. | 10 |
Citation
Yongyou Zhang
CKS2 (CDC28 protein kinase regulatory subunit 2)
Atlas Genet Cytogenet Oncol Haematol. 2010-02-01
Online version: http://atlasgeneticsoncology.org/gene/40093/cks2
