CKS1B (CDC28 protein kinase regulatory subunit 1B)

2009-09-01   Yongyou Zhang 

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




Atlas Image
Genomic organization of the CKS1B gene.


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.


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.


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


Atlas Image
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).


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


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


Cytoplasm and nucleus.


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


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


Pubmed IDLast YearTitleAuthors
150145022004Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase.Bashir T et al
86013101996Crystal structure and mutational analysis of the human CDK2 kinase complex with cell cycle-regulatory protein CksHs1.Bourne Y et al
195336832010The 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
86978181996Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22.Demetrick DJ et al
174997942007Increased SKP2 and CKS1 gene expression contributes to the progression of human urothelial carcinoma.Kawakami K et al
155794562004Role of Cks1 overexpression in oral squamous cell carcinomas: cooperation with Skp2 in promoting p27 degradation.Kitajima S et al
183719352008Fluoxetine mediates G0/G1 arrest by inducing functional inhibition of cyclin dependent kinase subunit (CKS)1.Krishnan A et al
184981312008Aberrant expression of Cks1 and Cks2 contributes to prostate tumorigenesis by promoting proliferation and inhibiting programmed cell death.Lan Y et al
189221572008Prognostic implication of p27Kip1, Skp2 and Cks1 expression in renal cell carcinoma: a tissue microarray study.Liu Z et al
186257202008Cyclin-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
128272072003Cks1-dependent proteasome recruitment and activation of CDC20 transcription in budding yeast.Morris MC et al
192962972009The expression and prognostic significance of Cks1 in salivary cancer.Nagler RM et al
165724262006Tissue array analysis of expression microarray candidates identifies markers associated with tumor grade and outcome in serous epithelial ovarian cancer.Ouellet V et al
22274111990Human cDNAs encoding homologs of the small p34Cdc28/Cdc2-associated protein of Saccharomyces cerevisiae and Schizosaccharomyces pombe.Richardson HE et al
157173222005The prognostic impact of the ubiquitin ligase subunits Skp2 and Cks1 in colorectal carcinoma.Shapira M et al
161681192005The expression of the ubiquitin ligase subunit Cks1 in human breast cancer.Slotky M et al
114633882001A CDK-independent function of mammalian Cks1: targeting of SCF(Skp2) to the CDK inhibitor p27Kip1.Spruck C et al
191619792009Role of Cks1 amplification and overexpression in breast cancer.Wang XC et al
180564672007Cks1 regulates cdk1 expression: a novel role during mitotic entry in breast cancer cells.Westbrook L et al
155139122004Direct 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


dbSNP: 1163
ClinVar: 1163
TCGA: ENSG00000173207


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Small cell lung cancerKEGGko05222
Pathways in cancerKEGGhsa05200
Small cell lung cancerKEGGhsa05222
Cell CycleREACTOMER-HSA-1640170
Cell Cycle, MitoticREACTOMER-HSA-69278
Mitotic G1-G1/S phasesREACTOMER-HSA-453279
Cyclin D associated events in G1REACTOMER-HSA-69231
G1/S TransitionREACTOMER-HSA-69206
Cyclin E associated events during G1/S transitionREACTOMER-HSA-69202
SCF(Skp2)-mediated degradation of p27/p21REACTOMER-HSA-187577
Cyclin A:Cdk2-associated events at S phase entryREACTOMER-HSA-69656

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
150145022004Control of the SCF(Skp2-Cks1) ubiquitin ligase by the APC/C(Cdh1) ubiquitin ligase.189
184719752008Cdc20 and Cks direct the spindle checkpoint-independent destruction of cyclin A.92
203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
173036952007CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms.52
209309462010Over-expression of CKS1B activates both MEK/ERK and JAK/STAT3 signaling pathways and promotes myeloma cell drug-resistance.49
174642902007Myc targets Cks1 to provoke the suppression of p27Kip1, proliferation and lymphomagenesis.44
169242412007Mutant B-RAF signaling and cyclin D1 regulate Cks1/S-phase kinase-associated protein 2-mediated degradation of p27Kip1 in human melanoma cells.34
161681192005The expression of the ubiquitin ligase subunit Cks1 in human breast cancer.33
161886522005Amplification and overexpression of CKS1B at chromosome band 1q21 is associated with reduced levels of p27Kip1 and an aggressive clinical course in multiple myeloma.31
216975112012Cyclin-dependent kinase subunit (Cks) 1 or Cks2 overexpression overrides the DNA damage response barrier triggered by activated oncoproteins.29


Yongyou Zhang

CKS1B (CDC28 protein kinase regulatory subunit 1B)

Atlas Genet Cytogenet Oncol Haematol. 2009-09-01

Online version: