CKS1B (CDC28 protein kinase regulatory subunit 1B)

2009-09-01 Yongyou Zhang Affiliation

Case Western Reserve University, 2103 Cornell Rd, WRB-3101, Cleveland, Ohio 44106, USA

Identity

HGNC

CKS1B

LOCATION

1q21.3

LOCUSID

1163

ALIAS

CKS1,PNAS-16,PNAS-18,ckshs1

DNA/RNA

Genomic organization of the CKS1B gene.

Description

Three exons, spans approximately 4.61 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 of approximately 1.8 kb. There are two transcript variants for CKS1B gene. The variant 2 uses a different splice site at the 3 end of the first exon compared to variant 1. There is no evidence that variant 2 encodes a protein.

Pseudogene

4 processed, non-expressed, pseudogenes in human genome.

Proteins

The side chains of residues of CKS1b in the binding sites for Cdk2, Skp2 and phosphorylated substrate are shown, with residues in the Cdk2-binding site in green, in the phosphate-binding site in blue, and the Skp2-binding site in red. (The structure figure modified from the origin paper: Markus A. Seeliger et al, Role of Conformational Heterogeneity in Domain Swapping and Adapter Function of the Cks Proteins. J. Biol. Chem., Vol. 280, Issue 34, 30448-30459, August 26, 2005).

Description

The open reading frame encodes a 79 amino acid protein, with an estimated molecular weight of approximately 9660 Da.

Expression

Basical level expression in all mammalian cell and aberrant expression in cancer cell.

Localisation

Cytoplasm and nucleus.

Function

CKS1B protein binds to the catalytic subunit of the cyclin dependent kinases and is essential for their biological function of cell cycle control.

Schematic of the regulation of cell cycle by the CKS1B. CKS1B associates with the p27kip1-Cdk/cyclin complex, induces the formation of the p27kip1-SCF ubiquitin ligase complex, triggers degradation of p27kip1, and signals cells to undergo the G1/S transition by releasing and activating the Cdk/cyclin A/E complexes. CycE/A, cyclin E or Cyclin A; Ub, ubiquitin.

Homology

The CKS1B proteins are evolutionary conserved. Mammalian cells express two well-conserved members, like the human CKS1B and CKS2 proteins. The CKSB1B protein is highly conserved across species.

Implicated in

Entity name

Cancer

Note

The expression of CKS1B is elevaled in multiple cancer, including breast cancer, lymphoma, myeloma, colon cancer, prostate cancer, lung cancer, renal carcinoma, oesophageal squamous cell carcinoma, salivary cancer, serous ovarian cancer, bladder cancer, urothelial carcinoma et al.

Prognosis

Overexpression of CKS1B is associated with poor prognosis in multiple cancer, including myeloma, breast cancer, lymphoma, renal carcinoma, ovarian cancer et al.

Oncogenesis

Amplification and overexpression of CKS1B were strongly associated with lymph node metastasis and poor prognosis in breast, salivary cancer and oesophageal squamous cell carcinoma. Generally, CKS1B is an essential factor in facilitating Skp2-dependent degradation of p27. In breast cancer cell, overexpression of CKS1B may inhibit the apoptosis through the MEK-Erk pathway. All of these suggest that CKS1B alterations may have a significant biological role in the tumorigenesis in different tissue and the novel therapeutic strategy for cancer through inhibiting the CKS1B activity. Therefore, disruption of Skp2-CKS1B assembly or down-regulation of CKS1B expression may be used for cancer therapy.

Article Bibliography

Pubmed ID	Last Year	Title	Authors
15014502	2004	Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase.	Bashir T et al
8601310	1996	Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1.	Bourne Y et al
19533683	2010	The degradation of cell cycle regulators by SKP2/CKS1 ubiquitin ligase is genetically controlled in rodent liver cancer and contributes to determine the susceptibility to the disease.	Calvisi DF et al
8697818	1996	Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22.	Demetrick DJ et al
17499794	2007	Increased SKP2 and CKS1 gene expression contributes to the progression of human urothelial carcinoma.	Kawakami K et al
15579456	2004	Role of Cks1 overexpression in oral squamous cell carcinomas: cooperation with Skp2 in promoting p27 degradation.	Kitajima S et al
18371935	2008	Fluoxetine mediates G0/G1 arrest by inducing functional inhibition of cyclin dependent kinase subunit (CKS)1.	Krishnan A 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
18922157	2008	Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study.	Liu Z 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
12827207	2003	Cks1-dependent proteasome recruitment and activation of CDC20 transcription in budding yeast.	Morris MC et al
19296297	2009	The expression and prognostic significance of Cks1 in salivary cancer.	Nagler RM et al
16572426	2006	Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer.	Ouellet V et al
2227411	1990	Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe.	Richardson HE et al
15717322	2005	The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma.	Shapira M et al
16168119	2005	The expression of the ubiquitin ligase subunit Cks1 in human breast cancer.	Slotky M et al
11463388	2001	A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1.	Spruck C et al
19161979	2009	Role of Cks1 amplification and overexpression in breast cancer.	Wang XC et al
18056467	2007	Cks1 regulates cdk1 expression: a novel role during mitotic entry in breast cancer cells.	Westbrook L et al
15513912	2004	Direct cell cycle regulation by the fibroblast growth factor receptor (FGFR) kinase through phosphorylation-dependent release of Cks1 from FGFR substrate 2.	Zhang Y et al

Other Information

Locus ID:

NCBI: 1163
MIM: 116900
HGNC: 19083
Ensembl: ENSG00000173207

Variants:

dbSNP: 1163
ClinVar: 1163
TCGA: ENSG00000173207
COSMIC: CKS1B

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000173207	ENST00000308987	P61024
ENSG00000173207	ENST00000308987	Q5T178
ENSG00000173207	ENST00000368436	Q5T179
ENSG00000173207	ENST00000368439	Q9BZU3

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Small cell lung cancer	KEGG	ko05222
Pathways in cancer	KEGG	hsa05200
Small cell lung cancer	KEGG	hsa05222
Cell Cycle	REACTOME	R-HSA-1640170
Cell Cycle, Mitotic	REACTOME	R-HSA-69278
Mitotic G1-G1/S phases	REACTOME	R-HSA-453279
G1 Phase	REACTOME	R-HSA-69236
Cyclin D associated events in G1	REACTOME	R-HSA-69231
G1/S Transition	REACTOME	R-HSA-69206
Cyclin E associated events during G1/S transition	REACTOME	R-HSA-69202
SCF(Skp2)-mediated degradation of p27/p21	REACTOME	R-HSA-187577
S Phase	REACTOME	R-HSA-69242
Cyclin A:Cdk2-associated events at S phase entry	REACTOME	R-HSA-69656

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
35174774	2022	Regulation of microRNA miR-197-3p/CDC28 protein kinase regulatory subunit 1B (CKS1B) axis by Circular RNA hsa_circ_0000285 promotes glioma progression.	5
35174774	2022	Regulation of microRNA miR-197-3p/CDC28 protein kinase regulatory subunit 1B (CKS1B) axis by Circular RNA hsa_circ_0000285 promotes glioma progression.	5
32908255	2021	The survival impact of CKS1B gains or amplification is dependent on the background karyotype and TP53 deletion status in patients with myeloma.	4
32960462	2021	CKS1B promotes cell proliferation and invasion by activating STAT3/PD-L1 and phosphorylation of Akt signaling in papillary thyroid carcinoma.	5
34702937	2021	Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1.	0
34845438	2021	A Pan-Cancer Analysis of Clinical Prognosis and Immune Infiltration of CKS1B in Human Tumors.	3
32908255	2021	The survival impact of CKS1B gains or amplification is dependent on the background karyotype and TP53 deletion status in patients with myeloma.	4
32960462	2021	CKS1B promotes cell proliferation and invasion by activating STAT3/PD-L1 and phosphorylation of Akt signaling in papillary thyroid carcinoma.	5
34702937	2021	Establishment of high-throughput screening HTRF assay for identification small molecule inhibitors of Skp2-Cks1.	0
34845438	2021	A Pan-Cancer Analysis of Clinical Prognosis and Immune Infiltration of CKS1B in Human Tumors.	3
30497779	2019	Cks1 regulates human hepatocellular carcinoma cell progression through osteopontin expression.	6
30605238	2019	Prognostic and clinicopathological significance of Cks1 in cancer: Evidence from a meta-analysis.	5
31717435	2019	MicroRNA-1258 Inhibits the Proliferation and Migration of Human Colorectal Cancer Cells through Suppressing CKS1B Expression.	23
30497779	2019	Cks1 regulates human hepatocellular carcinoma cell progression through osteopontin expression.	6
30605238	2019	Prognostic and clinicopathological significance of Cks1 in cancer: Evidence from a meta-analysis.	5

Citation

Yongyou Zhang

CKS1B (CDC28 protein kinase regulatory subunit 1B)

Atlas Genet Cytogenet Oncol Haematol. 2009-09-01

Online version: http://atlasgeneticsoncology.org/gene/40092/cks1b