| 2008 |
Simultaneous disruption of CKS1 and CKS2 causes embryonic lethality at the morula stage; RNAi-mediated depletion in MEFs causes G2 arrest followed by rereplication and polyploidy, attributable to impaired transcription of CCNB1, CCNA2, and CDK1 genes. Restoration of cyclin B1 expression rescues the arrest. Cks2 is recruited to chromatin and to promoter regions/open reading frames of genes requiring Cks function with cell-cycle periodicity correlating with their transcription. |
Double-knockout mouse genetics, RNAi in MEFs and HeLa cells, rescue experiments with cyclin B1, chromatin immunoprecipitation (ChIP) |
Molecular and cellular biology |
High |
18625720
|
| 2011 |
Overexpression of CKS2 (or CKS1) confers partial resistance to CDK2 inhibitory tyrosine phosphorylation mediated by the intra-S-phase checkpoint, allowing continued DNA replication under replicative stress; this is dependent on binding of CKS2 to CDK2. |
Overexpression in human mammary epithelial and breast cancer cell lines, intra-S-phase checkpoint assays, analysis of CDK2 phosphorylation status |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
21697511
|
| 2012 |
CKS2 counteracts CKS1 and stabilizes p27 (CDKN1B); in Cks2-knockout mouse cells, unopposed CKS1 activity leads to loss of p27, resulting in unrestricted cyclin A/CDK2 activity, shortened cell cycle, increased replication fork velocity, and DNA damage. In vivo, Cks2-null cortical progenitor cells are impaired in differentiation into mature neurons. |
Cks2-knockout mouse model, analysis of p27 levels, cyclin A/CDK2 activity assays, DNA fiber assays for replication fork velocity, in vivo neuronal differentiation analysis |
Developmental cell |
High |
22898779
|
| 2008 |
In prostate cancer cells, knockdown of CKS2 induces programmed cell death and inhibits tumorigenicity, while forced overexpression promotes cell population growth, indicating CKS2 protects prostate tumor cells from apoptosis. |
siRNA knockdown, cDNA overexpression, cell growth assays, anchorage-independent growth assay, tumorigenicity assay |
International journal of cancer |
Medium |
18498131
|
| 2008 |
CKS2 overexpression in gastric cancer cells downregulates p53 and p21(cip1) and increases cell growth, while CKS2-siRNA increases tumor suppressor expression and decreases cell growth. GFP-CKS2 localization experiments were performed. |
GFP-CKS2 overexpression (cellular localization), CKS2-siRNA knockdown, Western blot for p53 and p21, cell proliferation assays |
Journal of cancer research and clinical oncology |
Medium |
19034516
|
| 2017 |
CKS1 and CKS2 proteins physically interact with both the MllN and MllC subunits of Mll1 (Mixed-lineage leukaemia 1), and together the CKS proteins define Mll1 protein levels throughout the cell cycle. |
Co-immunoprecipitation (co-IP), cell-cycle-staged protein level analysis, small-molecule inhibitors (MLN4924 and C1) to modulate CKS-dependent protein degradation |
Biochimica et biophysica acta. Molecular cell research |
Medium |
28939057
|
| 2019 |
CKS2 forms a complex with mitochondrial single-stranded DNA binding protein SSBP1 and CDK1 in the mitochondria of cervical cancer cells and tumor samples; the CKS2-SSBP1 complex abundance shows cell cycle regulation consistent with mitochondrial DNA replication activity, linking CKS2 to oxidative phosphorylation regulation. Cytoplasmic (mitochondrial) CKS2 expression adds to nuclear CKS2 prognostic impact. |
In situ proximity ligation assay (PLA) in tumor samples and cell lines, flow cytometry for cell cycle staging, immunohistochemistry for subcellular localization |
Neoplasia (New York, N.Y.) |
Medium |
30856376
|
| 2013 |
miR-26a directly targets the 3'-UTR of CKS2 mRNA and represses CKS2 expression; downregulation of CKS2 by miR-26a or siRNA causes G2-phase arrest and reduces cell growth in papillary thyroid carcinoma cells. CKS2-dependent downstream genes include cyclin B1, cyclin A, cdk1, bcl-xl, and Akt. |
Luciferase reporter assay for direct 3'-UTR targeting, anti-miR/mimic transfection, siRNA knockdown, Western blot, cell cycle analysis, xenograft in SCID mice |
PloS one |
Medium |
23861775
|
| 2016 |
miR-7 directly binds the 3'-UTR of CKS2 and negatively regulates CKS2 protein expression; CKS2 knockdown suppresses thyroid papillary cancer cell proliferation, migration, and invasion and causes G0/G1 arrest; cyclin B1 and CDK1 are regulated downstream of the miR-7/CKS2 axis. |
Dual-luciferase reporter assay, Western blot, siRNA knockdown, MTT assay, colony formation, migration/invasion assays, cell cycle analysis |
International journal of oncology |
Medium |
27633373
|
| 2022 |
CKS2 interacts with DUTPase (DUT) in tongue squamous cell carcinoma cells; CKS2 knockdown does not alter DUTPase expression but reduces its nuclear distribution, indicating CKS2 modulates subcellular localization of DUTPase to promote cell cycle progression. |
Co-immunoprecipitation (co-IP), immunofluorescence co-localization, siRNA knockdown, cell cycle analysis |
Journal of oral pathology & medicine |
Medium |
33107644
|
| 2022 |
E2F1 transcription factor directly binds the CKS2 promoter and enhances CKS2 expression; CKS2 in turn regulates the PI3K-AKT/PTEN signaling pathway in retinoblastoma cells. Depletion of CKS2 reduced proliferation, DNA replication, and xenograft tumor growth; re-expression of CKS2 rescued these phenotypes. |
ChIP-seq (E2F1 binding to CKS2 promoter), RNA-seq, siRNA knockdown, rescue overexpression, xenograft tumor model, Western blot for PTEN/AKT |
Cell death & disease |
Medium |
36096885
|
| 2022 |
CKS2 overexpression activates TGFβ/SMAD signaling by inducing nucleocytoplasmic translocation of SMAD2/3 and upregulating downstream targets; this promotes EMT-like processes in glioma cells. TGFβ inhibitor LY2157299 or SMAD4 siRNA reverses CKS2-induced tumor-promoting effects. |
CKS2 siRNA knockdown and overexpression, Western blot and immunofluorescence for SMAD2/3 translocation and EMT markers, pharmacological inhibition (LY2157299), SMAD4 siRNA epistasis |
Cancer medicine |
Medium |
36284444
|
| 2022 |
Parkin (PARK2) E3 ubiquitin ligase overexpression reduces CKS2 protein levels in clear cell renal cell carcinoma cells, leading to decreased migration and invasion; mutation of the Parkin catalytic domain abolishes the effect on migration, indicating Parkin regulates CKS2 through its ubiquitin ligase activity. |
PARK2 overexpression and catalytic-domain mutagenesis, mass spectrometry proteomics, CKS2 siRNA knockdown, migration/invasion functional assays |
International journal of oncology |
Medium |
35059737
|
| 2015 |
Depletion of CKS2 (or CKS1) in HepG2 hepatocellular carcinoma cells decreases phospho-Akt and phospho-GSK-3β protein levels, implicating CKS2 in PI3K/Akt signaling to promote cell survival. |
siRNA knockdown, Western blot for p-Akt and p-GSK-3β, cell proliferation and apoptosis assays |
Oncology reports |
Low |
26531156
|
| 2023 |
DLX4 knockdown in NSCLC cells suppresses YB-1 expression, which in turn suppresses CKS2 expression, thereby inhibiting tumor cell growth and causing cell cycle arrest, placing YB-1 as an intermediate regulator upstream of CKS2. |
siRNA knockdown of DLX4, Western blot for YB-1 and CKS2, cell viability and cell cycle assays |
Open life sciences |
Low |
37744456
|
| 2023 |
ELK1 transcription factor regulates transcription of the CKS2 gene in pancreatic cancer cells; CKS2 knockdown increases Bax, caspase-3, p53, p21, and GADD45α and decreases Bcl-2, Cyclin B1, CDK1, Cyclin A, and Cdc25C expression. |
ELK1 functional analysis, CKS2 siRNA knockdown and overexpression, Western blot for cell cycle and apoptosis proteins, xenograft tumor model |
Molecular carcinogenesis |
Low |
37642304
|
| 2024 |
CKS2 promotes autophagy-mediated glutathione (GSH) metabolic reprogramming in colon cancer cells, increasing resistance to ferroptosis; CKS2 knockdown enhances Erastin-induced ferroptosis and downregulates GPX4 expression, while CKS2 overexpression has the opposite effect. This mechanism is operative both in vitro and in vivo. |
CKS2 knockdown and overexpression, transmission electron microscopy for autophagy, BODIPY/DCFH-DA staining for lipid peroxidation/ROS, GSH assay, Western blot for GPX4 and autophagy markers, xenograft model |
Molecular medicine (Cambridge, Mass.) |
Medium |
39548421
|
| 2025 |
CKS2 overexpression reduces PTEN protein levels, thereby inhibiting PIP3 degradation and activating PI3K/AKT signaling in bladder cancer cells; additionally, CKS2 promotes phosphorylation and degradation of p27(Kip1) at Thr187, contributing to cell cycle deregulation. PI3K inhibitor LY294002 reverses CKS2-induced proliferation and metastasis. |
CKS2 siRNA knockdown and overexpression, Western blot for PTEN/p-AKT/p27, pharmacological inhibition with LY294002, functional assays (proliferation, migration, invasion) |
Cell cycle (Georgetown, Tex.) |
Medium |
41200902
|
| 2025 |
CKS2 directly interacts with thioredoxin (TXN) by co-immunoprecipitation in multiple myeloma cells; TXN appears to function as an upstream regulatory factor governing CKS2 protein stability. CKS2 depletion modulates proliferation and apoptosis via the PTEN/AKT/mTOR signaling axis. |
Co-immunoprecipitation, confocal immunofluorescence, AlphaFold2 structural modeling, CKS2 knockdown and overexpression, Western blot for PTEN/AKT/mTOR pathway components, xenograft model |
Journal of Cancer |
Low |
40092696
|
| 2025 |
DNMT1-mediated DNA hypermethylation of the SOX21 promoter silences SOX21, a transcriptional repressor of CKS2; thus DNMT1 indirectly upregulates CKS2 in gastric cancer. ChIP and dual-luciferase reporter assays confirmed SOX21 directly binds the CKS2 promoter and represses its transcription. |
ChIP assay, dual-luciferase reporter assay, qMSP for DNA methylation, SOX21 rescue experiments, sh-DNMT1 with SOX21 silencing epistasis, xenograft model |
BMC cancer |
Medium |
40676553
|
| 2026 |
METTL3-mediated m6A modification of CKS2 mRNA increases its stability in an IGF2BP1-dependent manner; IGF2BP1 directly binds m6A-modified CKS2 transcripts to maintain their stability, and METTL3 overexpression partially rescues the suppressive effects of CKS2 silencing on osteosarcoma cells. |
RIP (RNA immunoprecipitation), MeRIP (m6A-specific RIP), mRNA stability assays, Western blot, bioinformatics correlation, rescue experiments |
International reviews of immunology |
Medium |
41822976
|
| 2025 |
CKS2 knockdown decreases phosphorylation of CDK1 (Thr161) and Cyclin B1 (Ser126) in neuroblastoma cells, suggesting CKS2 promotes cell division signaling through the CDK1/Cyclin B1 complex. Treatment with importazole (importin-β inhibitor) causes CKS2 to accumulate in the cytoplasm rather than the nucleus, inhibiting proliferation; combining CKS2 knockdown with importazole produces synergistic anti-tumor effects. |
CKS2 siRNA knockdown, Western blot for CDK1/Cyclin B1 phosphorylation, importazole pharmacological treatment, subcellular fractionation/localization, xenograft tumor model |
Neurochemical research |
Medium |
40696188
|
| 2025 |
MRTF-SRF transcriptional activity is required for maintaining CKS2 protein levels; cells lacking MRTFs or SRF exhibit decreased CKS2 and CDK1 protein levels along with elevated p27, leading to slow proliferation; MRTF-A re-expression fully restores CKS2 levels and rescues the proliferative defect. |
MRTF/SRF knockout cells, Western blot for CKS2/CDK1/p27, MRTF-A rescue re-expression, serum deprivation controls, ROCK/Myosin ATPase inhibitor treatment |
bioRxivpreprint |
Medium |
|
| 2023 |
In hematopoietic stem cells, CKS1 and CKS2 regulate key signaling pathways (AKT, FOXO1, NFκB) as determined by combined transcriptome and proteome analysis of Cks1 and Cks2 knockout mice; these pathways together balance protein homeostasis and restrain reactive oxygen species to ensure healthy hematopoietic stem cell function. |
Cks1 and Cks2 knockout mouse models, transcriptomic and proteomic profiling, hematopoietic stem cell transplantation/reconstitution assays |
HemaSphere |
Medium |
36874381
|