Download Gene Section CKS2 (CDC28 protein kinase regulatory subunit 2)

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Gene Section
Review
CKS2 (CDC28 protein kinase regulatory subunit 2)
Yongyou Zhang
Case Western Reserve University, WRB-3101, 2103 Cornell Rd, Cleveland, OH 44106, USA (YZ)
Published in Atlas Database: February 2010
Online updated version : http://AtlasGeneticsOncology.org/Genes/CKS2ID40093ch9q22.html
DOI: 10.4267/2042/44906
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence.
© 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Description
Identity
The open reading frame encodes a 79 amino acid
protein, with an estimated molecular weight of
approximately 9860 Da.
Other names: CKSHS2
HGNC (Hugo): CKS2
Location: 9q22.2
Note: There is no evidence that CKS2 gene has
different transcript variant.
Expression
Basic level expression in all mammalian cells and
aberrant expression in cancer cells.
Localisation
DNA/RNA
Cytoplasm and nucleus.
Function
Transcription
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.
mRNA is 627 bp.
Homology
Pseudogene
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.
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.
1 processed, non-expressed, pseudogene in human
genome.
Protein
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.
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
Mutations
Note
Mutation of glutamine for glutamate 63 (E63Q),
1100
CKS2 (CDC28 protein kinase regulatory subunit 2)
Zhang Y
disrupted the essential biological function of the protein
and significantly reduced its ability to bind to cyclindependent kinases, but preserves protein structure and
assembly.
(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.
Implicated in
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.
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).
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).
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).
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).
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).
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).
Glioblastoma
Note
CKS2 was significantly up-regulated in primary
glioblastomas compared with the non-neoplastic brain
tissues (Scrideli et al., 2008).
Colon cancer
Note
CKS2 was reported significantly overexpressed in
microdissected invasive colon tumor cells compared
with adjacent normal epithelial cells
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
Meningioma
Note
This microarray-based expression profiling study
1101
CKS2 (CDC28 protein kinase regulatory subunit 2)
Zhang Y
bladder cancer through genome-wide gene
profiling. Oncol Rep. 2006 Sep;16(3):521-31
showed CKS2 is unregulated in atypical and anaplastic
meningiomas compared with benign meningiomas
(Fevre-Montange et al., 2009).
Lyng H, Brøvig RS, Svendsrud DH, Holm R, Kaalhus O,
Knutstad K, Oksefjell H, Sundfør K, Kristensen GB, Stokke T.
Gene expressions and copy numbers associated with
metastatic phenotypes of uterine cervical cancer. BMC
Genomics. 2006 Oct 20;7:268
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This article should be referenced as such:
Zhang Y. CKS2 (CDC28 protein kinase regulatory subunit 2).
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12):11001103.
Miller WR. Clinical, pathological, proliferative and molecular
responses associated with neoadjuvant aromatase inhibitor
Atlas Genet Cytogenet Oncol Haematol. 2010; 14(12)
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