HCSGD entry for CDK2
1. General information
| Official gene symbol | CDK2 |
|---|---|
| Entrez ID | 1017 |
| Gene full name | cyclin-dependent kinase 2 |
| Other gene symbols | p33(CDK2) |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000082 | G1/S transition of mitotic cell cycle | IEA TAS | biological_process |
| GO:0000085 | Mitotic G2 phase | TAS | biological_process |
| GO:0000086 | G2/M transition of mitotic cell cycle | NAS | biological_process |
| GO:0000278 | Mitotic cell cycle | TAS | biological_process |
| GO:0000307 | Cyclin-dependent protein kinase holoenzyme complex | IDA IEA | cellular_component |
| GO:0000781 | Chromosome, telomeric region | IEA | cellular_component |
| GO:0000793 | Condensed chromosome | IEA | cellular_component |
| GO:0000805 | X chromosome | IEA | cellular_component |
| GO:0000806 | Y chromosome | IEA | cellular_component |
| GO:0004674 | Protein serine/threonine kinase activity | IEA | molecular_function |
| GO:0004693 | Cyclin-dependent protein serine/threonine kinase activity | IDA IEA TAS | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005524 | ATP binding | IEA | molecular_function |
| GO:0005634 | Nucleus | IDA IEA | cellular_component |
| GO:0005654 | Nucleoplasm | TAS | cellular_component |
| GO:0005667 | Transcription factor complex | IEA | cellular_component |
| GO:0005737 | Cytoplasm | IDA | cellular_component |
| GO:0005768 | Endosome | IDA | cellular_component |
| GO:0005813 | Centrosome | TAS | cellular_component |
| GO:0005829 | Cytosol | TAS | cellular_component |
| GO:0006260 | DNA replication | TAS | biological_process |
| GO:0006281 | DNA repair | IEA | biological_process |
| GO:0006813 | Potassium ion transport | IEA | biological_process |
| GO:0006977 | DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest | TAS | biological_process |
| GO:0007067 | Mitosis | IEA | biological_process |
| GO:0007126 | Meiosis | TAS | biological_process |
| GO:0007265 | Ras protein signal transduction | IEP | biological_process |
| GO:0007596 | Blood coagulation | TAS | biological_process |
| GO:0008284 | Positive regulation of cell proliferation | IDA | biological_process |
| GO:0015030 | Cajal body | IDA | cellular_component |
| GO:0016572 | Histone phosphorylation | IDA | biological_process |
| GO:0030332 | Cyclin binding | IDA IEA | molecular_function |
| GO:0031145 | Anaphase-promoting complex-dependent proteasomal ubiquitin-dependent protein catabolic process | TAS | biological_process |
| GO:0031571 | Mitotic G1 DNA damage checkpoint | TAS | biological_process |
| GO:0032298 | Positive regulation of DNA-dependent DNA replication initiation | IEA | biological_process |
| GO:0035173 | Histone kinase activity | IDA | molecular_function |
| GO:0045893 | Positive regulation of transcription, DNA-templated | IEA | biological_process |
| GO:0046872 | Metal ion binding | IEA | molecular_function |
| GO:0051298 | Centrosome duplication | TAS | biological_process |
| GO:0051439 | Regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle | TAS | biological_process |
| GO:0060968 | Regulation of gene silencing | IDA | biological_process |
| GO:0071732 | Cellular response to nitric oxide | TAS | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.9297857984 | 0.0043666236 | 0.9999902473 | 0.1344256140 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Down | -0.3765587742 |
| GSE13712_SHEAR | Up | 0.2224931577 |
| GSE13712_STATIC | Down | -0.0352300407 |
| GSE19018 | Up | 0.3205373178 |
| GSE19899_A1 | Down | -0.8838222689 |
| GSE19899_A2 | Down | -0.9992699850 |
| PubMed_21979375_A1 | Down | -1.1406550204 |
| PubMed_21979375_A2 | Down | -2.2457599758 |
| GSE35957 | Down | -0.9456341377 |
| GSE36640 | Down | -1.9037611897 |
| GSE54402 | Up | 0.1428083523 |
| GSE9593 | Down | -0.5871497519 |
| GSE43922 | Down | -0.1123587264 |
| GSE24585 | Up | 0.2320031553 |
| GSE37065 | Up | 0.0146299670 |
| GSE28863_A1 | Down | -0.6975003692 |
| GSE28863_A2 | Up | 0.2738849039 |
| GSE28863_A3 | Down | -0.4049985940 |
| GSE28863_A4 | Up | 0.2897717226 |
| GSE48662 | Down | -0.4841023556 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
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- Drugs
Not regulated by drugs
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-124-3p | MIMAT0000422 | MIRT004283 | Luciferase reporter assay//Western blot | Functional MTI | 19404929 |
| hsa-miR-124-3p | MIMAT0000422 | MIRT004283 | Proteomics;Microarray | Non-Functional MTI (Weak) | 18668037 |
| hsa-miR-103a-3p | MIMAT0000101 | MIRT004764 | Luciferase reporter assay//qRT-PCR//Western blot | Functional MTI | 20886090 |
| hsa-miR-885-5p | MIMAT0004947 | MIRT005461 | Luciferase reporter assay//Northern blot//qRT-PCR//Western blot | Functional MTI | 21233845 |
| hsa-miR-302d-3p | MIMAT0000718 | MIRT005672 | Luciferase reporter assay//Microarray//Northern blot//Western blot | Functional MTI | 21062975 |
| hsa-miR-376a-3p | MIMAT0000729 | MIRT007019 | Luciferase reporter assay | Functional MTI | 21556037 |
| hsa-miR-155-5p | MIMAT0000646 | MIRT020948 | Proteomics | Functional MTI (Weak) | 18668040 |
| hsa-miR-26b-5p | MIMAT0000083 | MIRT030063 | Microarray | Functional MTI (Weak) | 19088304 |
| hsa-miR-361-5p | MIMAT0000703 | MIRT044112 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-23b-3p | MIMAT0000418 | MIRT046257 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-10b-5p | MIMAT0000254 | MIRT047445 | CLASH | Functional MTI (Weak) | 23622248 |
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- mirRecord
MicroRNA name | mirBase ID | Target site number | MiRNA mature ID | Test method inter | MiRNA regulation site | Reporter target site | Pubmed ID |
|---|---|---|---|---|---|---|---|
| hsa-miR-302d-3p | MIMAT0000718 | 1 | hsa-miR-302d | {Western blot} | {overexpression by miRNA mimics tranfection} | 21062975 | |
| hsa-miR-302d-3p | MIMAT0000718 | 2 | hsa-miR-302d | {Western blot} | {overexpression by miRNA mimics tranfection} | 21062975 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 36 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27642518 | These non-coding RNAs can control cell cycle progression, cellular proliferation, and cellular survival impacting disorders linked to aging, cardiovascular disease, and atherosclerosis through pathways that involve cyclin-dependent kinase 2 (CDK2), cyclin-dependent kinase inhibitor 1 (p21), and mammalian forkhead transcription factors |
| 26690546 | Chloroquine alleviates etoposide-induced centrosome amplification by inhibiting CDK2 in adrenocortical tumor cells |
| 26690546 | Under such conditions, Chk2, cyclin A/CDK2 and ERK1/2 were aberrantly activated |
| 26690546 | Pharmacological inactivation of Chk2, CDK2 or ERK1/2 or depletion of CDK2 or Chk2 inhibited the centrosome amplification in ETO-treated ACT cells |
| 26690546 | Chloroquine alleviated CDK2 and ERK, but not Chk2, activation and thus inhibited centrosome amplification in either ETO- or hydroxyurea-treated ACT cells |
| 26690546 | In summary, we have demonstrated that chloroquine inhibited ACT cell growth and alleviated DNA damage-induced centrosome amplification by inhibiting CDK2 and ERK activity, thus preventing genomic instability and recurrence of ACT |
| 25693733 | Fucoidan also promoted the expression of cell cycle-associated proteins (cyclin E, Cdk2, cyclin D1, and Cdk4) in senescent ECFCs, significantly reversed cellular senescence, and increased the proliferation of ECFCs via the FAK, Akt, and ERK signaling pathways |
| 25149358 | CDK2 transcriptional repression is an essential effector in p53-dependent cellular senescence-implications for therapeutic intervention |
| 25149358 | The role of cyclin-dependent kinase 2 (CDK2) regulation has been evaluated in models of replicative senescence, but little is known regarding its role in other senescence settings |
| 25149358 | Using in vitro and in vivo models of DNA damage-and oncogene-induced cellular senescence, it was determined that activation of the tumor-suppressor protein p53 (TP53) resulted in repression of the CDK2 transcript that was dependent on intact RB |
| 25149358 | Ectopic CDK2 expression was sufficient to bypass p53-dependent senescence, and CDK2-specific inhibition, either pharmacologically (CVT313) or by use of a dominant-negative CDK2, was sufficient to induce early senescence |
| 25149358 | Pharmacologic inhibition of CDK2 in an in vivo model of pineal tumor decreased proliferation and promoted early senescence, and it also decreased tumor penetrance and prolonged time to tumor formation in animals lacking p53 |
| 25149358 | In conclusion, for both oncogene- and DNA damage-induced cellular senescence, CDK2 transcript and protein are decreased in a p53- and RB-dependent manner, and this repression is necessary for cell-cycle exit during senescence |
| 25149358 | IMPLICATIONS: These data show that CDK2 inhibition may be useful for cancer prevention in premalignant hyperproliferative lesions, as well as established tumors |
| 24473175 | These include nuclear topoisomerase I, relevant kinases (such as cyclin-dependent kinase 2) and the mitochondrial electron transport chain |
| 24254310 | In these assays, two truncated fragments of ING5 were found to inhibit the cyclin E and CDK2 expression |
| 23496142 | Transfection of early passage endothelial cells with miR-21 resulted in lower angiogenesis, and less cell proliferation mirrored by up-regulation of p21(CIP1) and down-regulation of CDK2 |
| 23496142 | These two cell-cycle regulators are indirectly regulated by miR-21 via its validated direct targets NFIB (Nuclear factor 1 B-type), a transcriptional inhibitor of p21(CIP) (1) , and CDC25A, which regulates CDK2 activity by dephosphorylation |
| 23254306 | Computational experiments reveal the efficacy of targeting CDK2 and CKIs for significantly lowering cellular senescence bar for potential cancer treatment |
| 23254306 | Lowering the threshold of cellular senescence, the process employed by cells to thwart abnormal cell proliferation, though inhibition of CDK2 or Skp2 (regulator of CDK inhibitors) has been recently suggested as a potential avenue for cancer treatment |
| 23254306 | We then investigate the effect of CDK2 deficiency on senescence in healthy cells, followed by effectiveness of CDK2 deficiency in triggering senescence in DNA damaged cells |
| 23254306 | For this, we focus on the behaviour of CycE, whose peak response indicates G1/S transition, for several reduced CDK2 levels in healthy as well as two DNA-damage conditions to calculate the probability (beta) or the percentage of CDK2 deficient cells passing G1/S checkpoint ((1-beta) indicates level of senescence) |
| 23254306 | Results show that 50% CDK2 deficiency can cause senescence in all healthy cells in a fairly uniform cell population; whereas, most healthy cells ( approximately 67%) in a heterogeneous population escape senescence |
| 23254306 | However, simultaneous variation of CDK2 and CKIs produces a dramatic reduction of damage cells passing the G1/S with CDK2&p27 combination causing senescence in almost all damaged cells |
| 22819841 | CDK2 differentially controls normal cell senescence and cancer cell proliferation upon exposure to reactive oxygen species |
| 22819841 | Sublethal doses of H(2)O(2) decreased the level of proliferating cell nuclear antigen (PCNA) in normal cells (including primary human dermal fibroblasts and IMR-90 cells) without affecting cyclin-dependent kinase 2 (CDK2) activity, leading to cell cycle arrest and subsequent senescence |
| 22819841 | In contrast, exposure of cancer cells (such as HeLa and MCF7 cells) to H(2)O(2) increased CDK2 activity with no accompanying change in the PCNA level, leading to cell proliferation |
| 22819841 | A CDK2 inhibitor, CVT-313, prevented H(2)O(2)-induced cancer cell proliferation |
| 22819841 | These results support the notion that the cyclin/CDK2/p21(Cip1)/PCNA complex plays an important role as a regulator of cell fate decisions |
| 22645767 | In contrast, the protein expressions of Cyclin E and CDK2 were obvious down-regulation |
| 22548705 | Interestingly, cell cycle exit was associated with repression of the Cyclin-dependent kinase Cdk2 |
| 22548705 | Upon tumor progression, both p18Ink4c-/- and p53-/- tumors showed increased Cdk2 expression |
| 22548705 | Inhibition of Cdk2 in cultured pre-tumorigenic and tumor cells of both backgrounds resulted in decreased proliferation and evidence of senescence |
| 22548705 | CONCLUSION: Our findings indicate that the p53 and the RB pathways play temporally distinct roles in senescence induction in Cyclin D1-expressing cells, and that Cdk2 inhibition plays a role in tumor suppression, and may be a useful therapeutic target |
| 21536883 | We identified a pharmacologic CDK2/cyclin E inhibitor, R-roscovitine (seliciclib; CYC202), which specifically reversed corticotroph expansion in live Tg:Pomc-Pttg embryos |
| 20818171 | These senescencesuppressing activities were critical for tumor progression, as deficiency in either Cdk2, telomerase or Miz1 reduced the onset of Myc-induced lymphoma in transgenic mice |
| 20818171 | Furthermore, Cdk2 inhibition re-activated the latent senescence program in Myc expressing cells |
| 20053783 | Under conditions where inhibition of both proliferation and c-Myc activity was observed, S2T1-6OTD treatment decreased the protein expression of the cell cycle activator cyclin-dependent kinase 2 and induced cell cycle arrest |
| 20010815 | Here, we uncover a role for Cdk2 (cyclin-dependent kinase 2) in suppressing Myc-induced senescence |
| 20010815 | Short-term activation of Myc promoted cell-cycle progression in either wild-type or Cdk2 knockout mouse embryo fibroblasts (MEFs) |
| 20010815 | Loss of Cdk2 also caused sensitization to Myc-induced senescence in pancreatic beta-cells or splenic B-cells in vivo, correlating with delayed lymphoma onset in the latter |
| 20010815 | Cdk2-/- MEFs also senesced upon ectopic Wnt signalling or, without an oncogene, upon oxygen-induced culture shock |
| 20010815 | However, unlike loss of Wrn, loss of Cdk2 did not enhance Myc-induced replication stress, implying that these proteins suppress senescence through different routes |
| 20010815 | Thus, although redundant for cell-cycle progression and development, Cdk2 has a unique role in suppressing oncogene- and/or stress-induced senescence |
| 20010815 | Pharmacological inhibition of Cdk2 induced Myc-dependent senescence in various cell types, including a p53-null human cancer cell line |
| 18843795 | We also show that overexpression of CDK4, or its homologue CDK6, but not the downstream kinase, CDK2, inhibited the ability of wild-type p16(INK4a) to promote cell cycle arrest and senescence |
| 18271016 | In this report, we show that depletion of EWS/FLI1 in Ewing's cell lines results in a senescence phenotype, a marked increase in expression of the G1/S regulatory proteins p27(kip1) and p57(kip2), and a significant decrease in cyclin D1 and CDK2 |
| 17975794 | The present article shows that olomoucine (OLO), a weak CDK2 inhibitor has new, unexpected activity |
| 15606011 | AIM: To explore the possible role of p21, cyclin E and cyclin-dependent kinase 2 (CDK2) in the protection of ginsenoside Rg1 against tert-butylhydroperoxide (t-BHP)-induced senescence in WI-38 cells |
| 15606011 | The levels of of p21, cyclin E and CDK2 protein were detected by Western blot |
| 15606011 | Simultaneously, compared with cells treated with t-BHP alone, Rg1 pretreatment markedly decreased the level of p21 protein and increased the levels of CDK2 and cyclin E |
| 15606011 | CONCLUSION: p21, cyclin E and CDK2 may be involved in the process of ginsenoside Rg1 protection against t-BHP-induced senescence in WI-38 cells |
| 13679081 | The cell cycle-associated proteins such as cyclin D1, cyclin E, CDK2, and CDK4, and kinase activities associated with CDK2 and CDK4 were increased in aged MASMC |
| 12939397 | Total inhibition of cyclin-dependent kinase 2 activity results in a cell cycle arrest on pRb loss and a nearly complete suppression of apoptosis |
| 12706118 | Mutant p53 can delay growth arrest and loss of CDK2 activity in senescing human fibroblasts without reducing p21(WAF1) expression |
| 12706118 | We have found up-regulated levels of the cyclin-dependent kinase 2 (cdk2) protein in HDF expressing 143(ala) mutant p53 as compared to senescent controls, together with an increase in p21-free cdk2 which, in conjunction with cyclin E, is able to form an active kinase which can phosphorylate the retinoblastoma protein |
| 11602203 | In addition, senescence is associated with increased binding of the cyclin-dependent kinase inhibitor (CDK-I) p16(INK4a) to CDK4, down-regulation of cyclin E protein levels (and consequent loss of cyclin E/CDK2 activity), underphosphorylation of the retinoblastoma protein RB and subsequent increased levels of E2F4-RB repressive complexes |
| 11287748 | On the other hand, treatment of young HDFs during the late G1 transition with a specific inhibitor of CDK2, roscovitine, blocked the induction of TK RNA expression |
| 11112337 | Regulation of cyclin-dependent kinase 2 activity by ceramide |
| 11112337 | Ceramide did not directly inhibit CDK2 in vitro but caused activation of p21, a major class of CDK-inhibitory proteins, and led to a greater association of p21 to CDK2 |
| 11112337 | Using purified protein phosphatases, we showed that ceramide activated both protein phosphatase 1 and protein phosphatase 2A activities specific for CDK2 in vitro |
| 11112337 | Further, calyculin A and okadaic acid, both potent protein phosphatase inhibitors, together almost completely reversed the effects of ceramide on CDK2 inhibition |
| 11112337 | Ceramide causes an increase in p21 association with CDK2 and through activation of protein phosphatases selectively regulates CDK2 |
| 10585280 | Here we present evidence that activation of a cAMP pathway correlates with multiple cellular changes in these cells: (1) increased expression of the transcription factor microphthalmia; (2) increased melanogenesis; (3) increased association of the cyclin-dependent kinase inhibitors (CDK-Is) p27(KIP1) and p16(INK4) with CDK2 and CDK4, respectively; (4) failure to phosphorylate the retinoblastoma protein (pRB); (5) decreased expression of E2F1, E2F2, and E2F4 proteins; (6) loss of E2F DNA-binding activity; and (7) phenotypic changes characteristic of senescent cells |
| 10585273 | Complex mechanisms underlying impaired activation of Cdk4 and Cdk2 in replicative senescence: roles of p16, p21, and cyclin D1 |
| 10585273 | In the present study, we have found a severe impairment in the activation of Cdk2 and Cdk4 in response to mitogens in senescent human fibroblasts and determined the molecular basis for this |
| 10585273 | Cdk2 protein was dramatically decreased in senescent cells and complexed primarily with cyclin D1 and p21 |
| 10585273 | Thus, one of the underlying molecular events involved in replicative senescence is the impaired activation of Cdk4 and Cdk2 due to increased binding of p16 to Cdk4 and increased association of Cdk2 with cyclin D1 and p21 |
| 10022898 | We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active |
| 9704925 | There was also an increased binding of p16 to the Cdk6 kinase in senescent cells, and a decreased Cdk6 as well as Cdk2 kinase activity |
| 9704925 | The levels of other G1 regulating proteins were also altered in the senescent cells, such as slightly elevated levels of p21/WAF1, and downregulation of Cdk2 and cyclinD3 |
| 9584157 | Cyclin D2 was also found to be associated with the cyclin-dependent kinases CDK2 and CDK4 but not CDK6 during growth arrest |
| 8853893 | The other two were novel E2F complexes that contained the cyclin-dependent kinase inhibitor p21 (cip1/WAF1/Sdi1/CAP20/PIC1) complexed with Rb/CDK2/cyclin E or with the Rb-related p107/CDK2/ cyclin D |
| 8853893 | Addition of purified p21 protein to the S-phase-specific cyclin A/ CDK2-p107-E2F complex from young cells dissociated cyclin A and CDK2 from p107/E2F, suggesting an additional novel function for p21 |
| 7615495 | Interestingly, when we determined DNA synthesis inhibitory activity of deletion mutants or point mutants that were unable to bind Cdk2 and/or PCNA, we found that loss of binding to PCNA did not affect inhibitory activity, whereas lack of Cdk2 binding greatly reduced the same |
| 7575495 | Failure to pass the R point may occur because senescent cells are unable to phosphorylate the retinoblastoma protein, owing to the accumulation of inactive complexes of cyclin E/Cdk2 and possibly cyclin D/Cdk4 |
| 7616677 | In addition, the protein levels of CDK2 and cyclin E are also extremely low, with an increased level of the p53-dependent p21 Cip 1 protein which inhibits the kinase activity of cyclins/CDKs by forming complexes |
| 7859744 | Amino acids 49-71 were involved in binding to Cdk2, and constructs deleted in this region expressed proteins that were unable to inhibit Cdk2 kinase activity in vitro |
| 8248208 | In contrast to early-passage cells in late G1 phase, senescent cells contained mainly underphosphorylated cyclin E and proportionally more unphosphorylated and inactive Cdk2, perhaps accounting for the low kinase activity |
| 8248208 | We also show that a majority of the Cdk2 in senescent cells, but not in early-passage cells, was complexed with cyclin D1 |
| 8248208 | Cyclin D1-Cdk2 complexes, severalfold enriched in senescent cells, contained exclusively unphosphorylated Cdk2 |
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