Affinage

CKS2

Cyclin-dependent kinases regulatory subunit 2 · UniProt P33552

Length
79 aa
Mass
9.9 kDa
Annotated
2026-06-09
44 papers in source corpus 23 papers cited in narrative 24 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CKS2 is an evolutionarily conserved CDK-associated subunit that, together with its paralog CKS1, is essential for cell-cycle progression and embryonic development, with combined loss causing morula-stage lethality and depletion producing G2 arrest, rereplication, and polyploidy through impaired transcription of CCNB1, CCNA2, and CDK1 (PMID:18625720). Mechanistically CKS2 is recruited to chromatin and to the promoters and open reading frames of these cell-cycle genes with periodicity matching their transcription (PMID:18625720), and it physically engages CDK2 to confer partial resistance to inhibitory tyrosine phosphorylation imposed by the intra-S-phase checkpoint, sustaining DNA replication under replicative stress (PMID:21697511). In a balance opposing CKS1, CKS2 stabilizes the CDK inhibitor p27/CDKN1B; its loss permits unopposed CKS1 activity, p27 degradation, unrestricted cyclin A/CDK2 activity, accelerated replication fork velocity, DNA damage, and impaired neuronal differentiation (PMID:22898779). CKS2 promotes CDK1/Cyclin B1 signaling, supporting phosphorylation of CDK1 (Thr161) and Cyclin B1, in a manner dependent on its importin-β-mediated nuclear import (PMID:40696188). Beyond the nucleus, CKS2 forms a mitochondrial complex with the single-stranded DNA-binding protein SSBP1 and CDK1, with cell-cycle-regulated abundance linking it to mitochondrial DNA replication and oxidative phosphorylation (PMID:30856376). CKS2 also engages downstream oncogenic signaling, reducing PTEN to activate PI3K/AKT and promoting p27 phosphorylation/degradation (PMID:41200902), and driving TGFβ/SMAD2/3 nucleocytoplasmic translocation to promote EMT-like processes (PMID:36284444). CKS2 expression is controlled at multiple layers: transcriptionally by E2F1 (PMID:36096885) and by MRTF-SRF, repressed by SOX21 (itself silenced by DNMT1-driven promoter hypermethylation) (PMID:40676553), post-transcriptionally stabilized by METTL3/IGF2BP1-mediated m6A modification (PMID:41822976) and targeted by miR-26a and miR-7 (PMID:23861775, PMID:27633373), and post-translationally turned over by the E3 ligase Parkin (PMID:35059737).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 2008 High

    Established that CKS proteins are essential for cell-cycle progression and act in transcription of mitotic cyclin/CDK genes, defining a chromatin-associated function beyond simple CDK binding.

    Evidence Double-knockout mouse genetics, RNAi in MEFs/HeLa with cyclin B1 rescue, and ChIP showing promoter/ORF recruitment

    PMID:18625720

    Open questions at the time
    • Molecular mechanism by which Cks2 promotes transcription at promoters/ORFs not defined
    • Direct DNA- versus protein-mediated recruitment not resolved
  2. 2008 Medium

    Linked CKS2 to tumor cell survival, showing it protects prostate tumor cells from apoptosis.

    Evidence siRNA knockdown and cDNA overexpression with growth, anchorage-independence, and tumorigenicity assays

    PMID:18498131

    Open questions at the time
    • Direct molecular target mediating anti-apoptotic effect not identified
    • Phenotype not connected to canonical CDK-binding function
  3. 2008 Medium

    Connected CKS2 to suppression of p53/p21 tumor suppressors, providing a route by which CKS2 drives proliferation.

    Evidence GFP-CKS2 localization, siRNA, and Western blot for p53/p21 in gastric cancer cells

    PMID:19034516

    Open questions at the time
    • Whether CKS2 regulates p53/p21 directly or through cell-cycle feedback unclear
    • No mechanism for p53 downregulation shown
  4. 2011 Medium

    Showed that CKS2 binding to CDK2 buffers the kinase against intra-S-phase checkpoint inhibition, explaining how CKS2 sustains replication under stress.

    Evidence Overexpression in mammary/breast cell lines with CDK2 phosphorylation analysis and checkpoint assays

    PMID:21697511

    Open questions at the time
    • Structural basis for resistance to inhibitory phosphorylation not defined
    • Single lab
  5. 2012 High

    Defined the CKS1-opposing role of CKS2 in stabilizing p27 to restrain cyclin A/CDK2 activity and safeguard replicative fidelity and differentiation.

    Evidence Cks2-knockout mouse cells with p27 measurements, CDK2 activity, DNA fiber assays, and in vivo cortical neuron differentiation

    PMID:22898779

    Open questions at the time
    • Biochemical mechanism by which CKS2 antagonizes CKS1-driven p27 turnover not resolved
    • Direct versus indirect effect on replication fork velocity unclear
  6. 2013 Medium

    Identified miR-26a as a direct repressor of CKS2 and mapped downstream cell-cycle/survival effectors, establishing post-transcriptional control of CKS2.

    Evidence Luciferase 3'-UTR reporter, anti-miR/mimic, siRNA, Western blot, and SCID xenografts in thyroid carcinoma

    PMID:23861775

    Open questions at the time
    • Whether downstream genes are direct CKS2 effectors not established
    • Single tumor context
  7. 2016 Medium

    Confirmed a second tumor-suppressive miRNA, miR-7, directly targeting CKS2, reinforcing miRNA-mediated regulation of the CKS2/CDK1/Cyclin B1 axis.

    Evidence Dual-luciferase reporter, siRNA, proliferation/migration/invasion and cell-cycle assays in thyroid cancer

    PMID:27633373

    Open questions at the time
    • Relative contribution of miR-7 versus other CKS2 regulators in vivo unknown
  8. 2017 Medium

    Expanded the CKS interactome to MLL1, showing CKS proteins set MLL1 levels across the cell cycle.

    Evidence Co-IP, cell-cycle-staged protein analysis, and degradation-modulating small molecules (MLN4924, C1)

    PMID:28939057

    Open questions at the time
    • Whether CKS2 directly targets MLL1 for degradation not resolved
    • CDK dependence of the interaction not tested
  9. 2019 Medium

    Revealed an unexpected mitochondrial role, placing CKS2 in a complex with SSBP1 and CDK1 linked to mtDNA replication and oxidative phosphorylation.

    Evidence In situ proximity ligation assay in tumors/cell lines, flow cytometry cell-cycle staging, IHC subcellular localization

    PMID:30856376

    Open questions at the time
    • Direct functional impact on mtDNA replication and OXPHOS not measured
    • How CKS2 is imported into mitochondria unknown
  10. 2022 Medium

    Identified E2F1 as a direct transcriptional activator of CKS2 and linked CKS2 to PI3K-AKT/PTEN signaling with in vivo validation.

    Evidence ChIP-seq, RNA-seq, siRNA with rescue, and xenografts in retinoblastoma

    PMID:36096885

    Open questions at the time
    • Direct mechanism by which CKS2 modulates PTEN/AKT not defined
  11. 2022 Medium

    Placed CKS2 upstream of TGFβ/SMAD signaling, showing it drives SMAD2/3 translocation and EMT-like behavior.

    Evidence Gain/loss-of-function with LY2157299 and SMAD4 siRNA epistasis in glioma

    PMID:36284444

    Open questions at the time
    • Mechanism connecting CKS2 to SMAD translocation unknown
    • Single tumor type
  12. 2022 Medium

    Established post-translational control of CKS2 by the E3 ligase Parkin, dependent on its catalytic activity.

    Evidence PARK2 overexpression, catalytic-domain mutagenesis, mass spectrometry, and migration/invasion assays in renal carcinoma

    PMID:35059737

    Open questions at the time
    • Direct ubiquitination of CKS2 by Parkin not demonstrated
    • Whether interaction is direct unknown
  13. 2022 Medium

    Identified DUTPase (DUT) as a CKS2 interactor whose nuclear localization, but not expression, depends on CKS2, expanding CKS2's role to controlling partner localization.

    Evidence Co-IP, immunofluorescence co-localization, siRNA, cell-cycle analysis in tongue carcinoma

    PMID:33107644

    Open questions at the time
    • Mechanism by which CKS2 directs DUT nuclear distribution unknown
  14. 2023 Medium

    Defined a physiological role for CKS1/CKS2 in hematopoietic stem cell homeostasis through AKT/FOXO1/NFκB signaling and ROS restraint.

    Evidence Cks1/Cks2 knockout mice with transcriptome/proteome profiling and HSC reconstitution assays

    PMID:36874381

    Open questions at the time
    • CKS2-specific versus CKS1-specific contributions not separated
    • Direct molecular targets in these pathways not identified
  15. 2024 Medium

    Linked CKS2 to ferroptosis resistance via autophagy-driven glutathione metabolic reprogramming and GPX4 maintenance.

    Evidence Gain/loss-of-function, TEM, lipid peroxidation/ROS staining, GSH assays, and xenografts in colon cancer

    PMID:39548421

    Open questions at the time
    • Mechanism connecting CKS2 to autophagy/GPX4 not defined
    • Single tumor context
  16. 2025 Medium

    Detailed a dual oncogenic mechanism whereby CKS2 lowers PTEN to activate PI3K/AKT and promotes Thr187 phosphorylation/degradation of p27.

    Evidence Gain/loss-of-function with LY294002 epistasis and Western blots in bladder cancer

    PMID:41200902

    Open questions at the time
    • Mechanism of PTEN downregulation by CKS2 not shown
    • Apparent contrast with CKS2-stabilizes-p27 role in non-tumor cells unresolved
  17. 2025 Medium

    Demonstrated DNMT1-mediated silencing of the CKS2 repressor SOX21, defining an epigenetic axis that upregulates CKS2.

    Evidence ChIP, dual-luciferase, qMSP, SOX21 rescue, and sh-DNMT1/SOX21 epistasis with xenografts in gastric cancer

    PMID:40676553

    Open questions at the time
    • Whether SOX21 loss is sufficient for CKS2-driven phenotypes not tested
  18. 2025 Medium

    Connected CKS2 function to importin-β-dependent nuclear import and CDK1/Cyclin B1 phosphorylation, with therapeutic synergy on import blockade.

    Evidence siRNA, Western blot for CDK1(Thr161)/Cyclin B1(Ser126), importazole treatment, fractionation, and xenografts in neuroblastoma

    PMID:40696188

    Open questions at the time
    • Import receptor that recognizes CKS2 not identified
    • Direct versus indirect effect on CDK1 phosphorylation unclear
  19. 2025 Low

    Identified TXN as a CKS2 interactor proposed to govern CKS2 protein stability, linking CKS2 to PTEN/AKT/mTOR signaling.

    Evidence Co-IP, confocal IF, AlphaFold2 modeling, knockdown/overexpression, and xenografts in multiple myeloma

    PMID:40092696

    Open questions at the time
    • TXN→CKS2 stability regulation described as suggestive, not demonstrated
    • Single Co-IP without reciprocal functional validation
  20. 2026 Medium

    Established m6A-based stabilization of CKS2 mRNA by METTL3 via the reader IGF2BP1, adding an epitranscriptomic regulatory layer.

    Evidence RIP, MeRIP, mRNA stability assays, and METTL3 rescue of CKS2 silencing in osteosarcoma

    PMID:41822976

    Open questions at the time
    • m6A site mapping on CKS2 transcript not detailed
    • Single tumor context
  21. 2025 Medium

    Placed MRTF-SRF transcriptional activity upstream of CKS2 protein levels, coupling cytoskeletal/serum signaling to CKS2-driven proliferation.

    Evidence MRTF/SRF knockout cells, MRTF-A rescue, Western blots, and ROCK/myosin inhibitor treatment (preprint)

    Open questions at the time
    • Direct MRTF-SRF binding to CKS2 promoter not shown
    • Preprint, not peer reviewed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the opposing CKS2 roles—stabilizing p27 to restrain CDK2 in normal cells versus promoting p27 degradation and PI3K/AKT activation in tumors—are reconciled mechanistically remains unresolved.
  • No structural or biochemical model integrating CKS2's context-dependent effects on p27
  • Determinants of CKS2 nuclear versus mitochondrial partitioning unknown
  • Direct substrates of CKS2-associated CDK activity not catalogued

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 3 GO:0060090 molecular adaptor activity 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005634 nucleus 2 GO:0005694 chromosome 1 GO:0005739 mitochondrion 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-69306 DNA Replication 2
Complex memberships
CKS2-SSBP1-CDK1 mitochondrial complex

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
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

Source papers

Stage 0 corpus · 44 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Cyclin-dependent kinase-associated proteins Cks1 and Cks2 are essential during early embryogenesis and for cell cycle progression in somatic cells. Molecular and cellular biology 106 18625720
2008 Aberrant expression of Cks1 and Cks2 contributes to prostate tumorigenesis by promoting proliferation and inhibiting programmed cell death. International journal of cancer 82 18498131
2011 Cyclin-dependent kinase subunit (Cks) 1 or Cks2 overexpression overrides the DNA damage response barrier triggered by activated oncoproteins. Proceedings of the National Academy of Sciences of the United States of America 67 21697511
2011 Cyclin-dependent kinase-associated protein Cks2 is associated with bladder cancer progression. The Journal of international medical research 55 21672358
2016 MicroRNA-7 inhibits proliferation, migration and invasion of thyroid papillary cancer cells via targeting CKS2. International journal of oncology 54 27633373
2013 miR-26a and its target CKS2 modulate cell growth and tumorigenesis of papillary thyroid carcinoma. PloS one 40 23861775
2015 CKS2 in human cancers: Clinical roles and current perspectives (Review). Molecular and clinical oncology 37 26137251
2012 The CDK subunit CKS2 counteracts CKS1 to control cyclin A/CDK2 activity in maintaining replicative fidelity and neurodevelopment. Developmental cell 35 22898779
2008 Upregulation of the cycline kinase subunit CKS2 increases cell proliferation rate in gastric cancer. Journal of cancer research and clinical oncology 34 19034516
2020 LINC00657/miR-26a-5p/CKS2 ceRNA network promotes the growth of esophageal cancer cells via the MDM2/p53/Bcl2/Bax pathway. Bioscience reports 25 32426838
2019 Mitochondrial Function of CKS2 Oncoprotein Links Oxidative Phosphorylation with Cell Division in Chemoradioresistant Cervical Cancer. Neoplasia (New York, N.Y.) 25 30856376
2018 EGFL7 promotes hepatocellular carcinoma cell proliferation and inhibits cell apoptosis through increasing CKS2 expression by activating Wnt/β-catenin signaling. Journal of cellular biochemistry 22 30129142
2015 Depletion of Cks1 and Cks2 expression compromises cell proliferation and enhance chemotherapy-induced apoptosis in HepG2 cells. Oncology reports 20 26531156
2022 High Expression of CKS2 Predicts Adverse Outcomes: A Potential Therapeutic Target for Glioma. Frontiers in immunology 19 35663965
2022 E2F1/CKS2/PTEN signaling axis regulates malignant phenotypes in pediatric retinoblastoma. Cell death & disease 17 36096885
2017 High-expressed CKS2 is associated with hepatocellular carcinoma cell proliferation through down-regulating PTEN. Pathology, research and practice 17 29487004
1996 Chromosomal mapping of the human genes CKS1 to 8q21 and CKS2 to 9q22. Cytogenetics and cell genetics 16 8697818
2022 Cyclin-dependent kinase subunit2 (CKS2) promotes malignant phenotypes and epithelial-mesenchymal transition-like process in glioma by activating TGFβ/SMAD signaling. Cancer medicine 15 36284444
2018 MicroRNA-26a inhibits proliferation and tumorigenesis via targeting CKS2 in laryngeal squamous cell carcinoma. Clinical and experimental pharmacology & physiology 15 29143362
2021 CKS2 Promotes the Growth in Non-Small-Cell Lung Cancer by Downregulating Cyclin-Dependent Kinase Inhibitor. Pathobiology : journal of immunopathology, molecular and cellular biology 14 34333494
2017 The Cks1/Cks2 axis fine-tunes Mll1 expression and is crucial for MLL-rearranged leukaemia cell viability. Biochimica et biophysica acta. Molecular cell research 14 28939057
2020 CKS2 modulates cell-cycle progression of tongue squamous cell carcinoma cells partly via modulating the cellular distribution of DUTPase. Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology 13 33107644
2010 Expression and biological-clinical significance of hTR, hTERT and CKS2 in washing fluids of patients with bladder cancer. BMC urology 10 20920335
2023 The CKS1/CKS2 Proteostasis Axis Is Crucial to Maintain Hematopoietic Stem Cell Function. HemaSphere 9 36874381
2023 Expression of CKS2 in Hepatocellular Carcinoma: Correlation with Survival Outcomes and Immune Microenvironment. Journal of hepatocellular carcinoma 8 37841370
2023 Aberrant expression of CKS2 induced by ELK1 contributes to malignant progression of pancreatic cancer. Molecular carcinogenesis 7 37642304
2024 CKS2 induces autophagy-mediated glutathione metabolic reprogramming to facilitate ferroptosis resistance in colon cancer. Molecular medicine (Cambridge, Mass.) 6 39548421
2023 Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2. Open life sciences 6 37744456
2022 Overexpression of Parkin in clear cell renal cell carcinoma decreases tumor aggressiveness by regulating CKS2 levels. International journal of oncology 6 35059737
2024 Biological functions and therapeutic potential of CKS2 in human cancer. Frontiers in oncology 4 39188686
2022 CKS2 and S100A12: Two Novel Diagnostic Biomarkers for Rheumatoid Arthritis. Disease markers 3 35789606
2025 Synergistic dual oncogenic role of CKS2 and ACAT2: Enhanced regulatory coherence and biomarker potential in adrenocortical carcinoma. Cancer genetics 2 41166795
2025 CKS2 Silencing Affects Proliferation and Apoptosis in Multiple Myeloma through the PTEN/ AKT/mTOR Pathway. Journal of Cancer 1 40092696
2025 DNMT1 blocks SOX21-repressed CKS2 transcription to promote gastric cancer progression. BMC cancer 1 40676553
2025 CKS2 promotes the malignant phenotypes of bladder cancer cells via PI3K/AKT signaling pathway activation. Cell cycle (Georgetown, Tex.) 1 41200902
2024 Unveiling CKS2: A Key Player in Aggressive B-Cell Lymphoma Progression and a Target for Synergistic Therapy. Cancer medicine 1 39560180
2007 Rat gene mapping in the post-genome sequencing era: the continued utility of cell hybrids to localize rat genes (Cks2, Ephb4, Fabp5, Il13ra1, Rpl10, Ssr4). Cytogenetic and genome research 1 17268179
2026 A multi-omics R-loop-linked risk program highlights CKS2-positive proliferative tumor cells as drivers of glioma growth. International immunopharmacology 0 41763168
2026 CKS2, regulated by METTL3, contributes to osteosarcoma progression in an IGF2BP1-dependent manner. International reviews of immunology 0 41822976
2026 Characterization of cyclotide Vdif A from Viola diffusa inhibits non-small cell lung cancer cells via regulation of CKS2. Phytomedicine : international journal of phytotherapy and phytopharmacology 0 41950730
2025 Nuclear Transport Receptor Importin-β Inhibition Enhances Cell Cycle Arrest Induced by CKS2 Knockdown to Suppress Neuroblastoma Progression. Neurochemical research 0 40696188
2025 CKS2 Mediates Hepatocellular Carcinoma Recurrence After Hepatic Ischemia-Reperfusion Injury Related to M2 Macrophages. Journal of inflammation research 0 40908951
2025 Facilitation of natural killer T-cell cytotoxic activity in uterine sarcoma via the CKS2-PI3K-AKT-MICA axis. Translational cancer research 0 40950663
2025 CKS2 is overexpressed in high-grade and recurrent meningiomas and functions as an oncogene via the CKS2/miR-26a/miR-101 axis. Computers in biology and medicine 0 41061391

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