HCSGD entry for CDK6

1. General information

Official gene symbolCDK6
Entrez ID1021
Gene full namecyclin-dependent kinase 6
Other gene symbolsPLSTIRE
Links to Entrez GeneLinks to Entrez Gene

2. Neighbors in the network

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3. Gene ontology annotation

GO ID

GO term

Evidence

Category

GO:0000082G1/S transition of mitotic cell cycleTASbiological_process
GO:0000278Mitotic cell cycleTASbiological_process
GO:0000307Cyclin-dependent protein kinase holoenzyme complexIDAcellular_component
GO:0001726RuffleIDAcellular_component
GO:0001954Positive regulation of cell-matrix adhesionIDAbiological_process
GO:0003323Type B pancreatic cell developmentIDAbiological_process
GO:0004693Cyclin-dependent protein serine/threonine kinase activityIDAmolecular_function
GO:0005515Protein bindingIPImolecular_function
GO:0005524ATP bindingIDAmolecular_function
GO:0005634NucleusIDAcellular_component
GO:0005737CytoplasmIDAcellular_component
GO:0005829CytosolTAScellular_component
GO:0006468Protein phosphorylationIDAbiological_process
GO:0007050Cell cycle arrestTASbiological_process
GO:0008285Negative regulation of cell proliferationTASbiological_process
GO:0009615Response to virusIEPbiological_process
GO:0010468Regulation of gene expressionIDA IMPbiological_process
GO:0014002Astrocyte developmentISSbiological_process
GO:0021542Dentate gyrus developmentISSbiological_process
GO:0021670Lateral ventricle developmentISSbiological_process
GO:0030332Cyclin bindingIPImolecular_function
GO:0042063GliogenesisIMPbiological_process
GO:0043697Cell dedifferentiationIMPbiological_process
GO:0045596Negative regulation of cell differentiationTASbiological_process
GO:0045638Negative regulation of myeloid cell differentiationIDAbiological_process
GO:0045646Regulation of erythrocyte differentiationIMPbiological_process
GO:0045668Negative regulation of osteoblast differentiationIDAbiological_process
GO:0045786Negative regulation of cell cycleIDAbiological_process
GO:0048146Positive regulation of fibroblast proliferationIMPbiological_process
GO:0048699Generation of neuronsISSbiological_process
GO:0050680Negative regulation of epithelial cell proliferationIMPbiological_process
GO:0051301Cell divisionIEAbiological_process
GO:2000145Regulation of cell motilityISSbiological_process
GO:2000773Negative regulation of cellular senescenceIDAbiological_process
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4. Expression levels in datasets

  • Meta-analysis result

p-value upp-value downFDR upFDR down
0.35101134840.02099348050.99999024730.2804920812

  • Individual experiment result
    ( "-" represent NA in the specific microarray platform )

Data sourceUp or downLog fold change
GSE11954Down-0.0559908463
GSE13712_SHEARUp0.3135134187
GSE13712_STATICUp0.0414567228
GSE19018Up0.6371590631
GSE19899_A1Down-0.6713415552
GSE19899_A2Down-0.5816241961
PubMed_21979375_A1Down-0.5731280502
PubMed_21979375_A2Down-0.6935374581
GSE35957Up0.9184850278
GSE36640Up0.4533960023
GSE54402Down-0.7616159680
GSE9593Up0.1904910202
GSE43922Down-0.4952636826
GSE24585Down-0.7684793124
GSE37065Down-0.2290882888
GSE28863_A1Down-0.2208836768
GSE28863_A2Up0.8885805375
GSE28863_A3Down-0.5529198244
GSE28863_A4Down-0.2653049824
GSE48662Up0.1619736446

5. Regulation relationships with compounds/drugs/microRNAs

  • Drugs

Name

Drug

Accession number

FlavopiridolDB03496 EXPT00998
(2S)-2-({6-[(3-amino-5-chlorophenyl)amino]-9-isopropyl-9H-purin-2-yl}amino)-3-methylbutan-1-olDB07379 -
3,7,3',4'-TETRAHYDROXYFLAVONEDB07795 -
PalbociclibDB09073 -

  • MicroRNAs

    • mirTarBase

MiRNA_name

mirBase ID

miRTarBase ID

Experiment

Support type

References (Pubmed ID)

hsa-miR-195-5pMIMAT0000461MIRT000224Reporter assay;Western blot;qRT-PCR;OtherFunctional MTI19441017
hsa-let-7a-5pMIMAT0000062MIRT000415CLASHFunctional MTI (Weak)23622248
hsa-miR-29a-3pMIMAT0000086MIRT000682qRT-PCR//Western blotFunctional MTI19850741
hsa-miR-29a-3pMIMAT0000086MIRT000682Luciferase reporter assay//qRT-PCR//Western blot//Reporter assay;Western blot;qRT-PCRFunctional MTI20086245
hsa-miR-29b-3pMIMAT0000100MIRT000684qRT-PCR//Luciferase reporter assay//Western blotFunctional MTI19850741
hsa-miR-29b-3pMIMAT0000100MIRT000684Luciferase reporter assay//qRT-PCR//Western blot//Reporter assay;Western blot;qRT-PCRFunctional MTI20086245
hsa-miR-34b-5pMIMAT0000685MIRT000762Luciferase reporter assayFunctional MTI19461653
hsa-miR-424-5pMIMAT0001341MIRT000938qRT-PCR//flow//Luciferase reporter assay//Western blotFunctional MTI18701644
hsa-miR-16-5pMIMAT0000069MIRT000939qRT-PCR//flow//Luciferase reporter assay//Western blotFunctional MTI18701644
hsa-miR-26a-5pMIMAT0000082MIRT006306Luciferase reporter assay//Western blotFunctional MTI22210897
hsa-miR-34a-5pMIMAT0000255MIRT001012qRT-PCR//Luciferase reporter assay//Western blot//Reporter assayFunctional MTI18406353
hsa-miR-34a-5pMIMAT0000255MIRT001012Luciferase reporter assayFunctional MTI19461653
hsa-miR-34a-5pMIMAT0000255MIRT001012qRT-PCR//Western blot//Luciferase reporter assayFunctional MTI19584398
hsa-miR-34a-5pMIMAT0000255MIRT001012Luciferase reporter assay//Western blot//MicroarrayFunctional MTI17914404
hsa-miR-34a-5pMIMAT0000255MIRT001012Luciferase reporter assay//qRT-PCR//Western blotFunctional MTI19773441
hsa-miR-34a-5pMIMAT0000255MIRT001012Western blot;OtherFunctional MTI21240262
hsa-miR-107MIMAT0000104MIRT001233Western blotFunctional MTI19407485
hsa-miR-107MIMAT0000104MIRT001233Flow//Immunoblot//Microarray//qRT-PCR//Western blotFunctional MTI19688090
hsa-miR-107MIMAT0000104MIRT001233Luciferase reporter assay//Microarray//Western blot//qRT-PCRFunctional MTI20833636
hsa-miR-107MIMAT0000104MIRT001233Western blot;qRT-PCRFunctional MTI21264532
hsa-miR-30a-3pMIMAT0000088MIRT001760Luciferase reporter assay//qRT-PCR//Western blot//Western blot;qRT-PCRFunctional MTI16239240
hsa-let-7b-5pMIMAT0000063MIRT002297Luciferase reporter assay//Microarray//Western blotFunctional MTI17699775
hsa-miR-21-5pMIMAT0000076MIRT002406SequencingFunctional MTI (Weak)20371350
hsa-miR-137MIMAT0000429MIRT002490Luciferase reporter assay//qRT-PCR//Western blotFunctional MTI18381414
hsa-miR-137MIMAT0000429MIRT002490Luciferase reporter assayFunctional MTI18577219
hsa-miR-137MIMAT0000429MIRT002490Western blotFunctional MTI20682795
hsa-miR-137MIMAT0000429MIRT002490Luciferase reporter assay//qRT-PCR//Western blotFunctional MTI21051724
hsa-miR-137MIMAT0000429MIRT002490Luciferase reporter assayFunctional MTI23178712
hsa-miR-124-3pMIMAT0000422MIRT002642ChIP-seq//Western blotFunctional MTI19435910
hsa-miR-124-3pMIMAT0000422MIRT002642Immunohistochemistry//Luciferase reporter assay//Microarray//qRT-PCR//Western blotFunctional MTI17308079
hsa-miR-124-3pMIMAT0000422MIRT002642Luciferase reporter assay//Western blotFunctional MTI18607543
hsa-miR-124-3pMIMAT0000422MIRT002642Luciferase reporter assayFunctional MTI17581274
hsa-miR-124-3pMIMAT0000422MIRT002642Luciferase reporter assayFunctional MTI18577219
hsa-miR-124-3pMIMAT0000422MIRT002642Luciferase reporter assay//qRT-PCR//Western blotFunctional MTI19843643
hsa-miR-124-3pMIMAT0000422MIRT002642MicroarrayFunctional MTI (Weak)18668037
hsa-miR-124-3pMIMAT0000422MIRT002642MicroarrayFunctional MTI (Weak)15685193
hsa-miR-29c-3pMIMAT0000681MIRT003200Luciferase reporter assay//qRT-PCR//Western blot//Reporter assay;Western blot;qRT-PCR;OtherFunctional MTI20086245
hsa-miR-449aMIMAT0001541MIRT003187Luciferase reporter assay//Microarray//qRT-PCR//Western blot//Reporter assay;Western blot;OtherFunctional MTI19833767
hsa-miR-26b-5pMIMAT0000083MIRT006307Luciferase reporter assay//Western blotFunctional MTI22210897
hsa-miR-34b-3pMIMAT0004676MIRT003579Luciferase reporter assay//Western blotFunctional MTI18768788
hsa-miR-185-5pMIMAT0000455MIRT004700Flow//Immunoblot//Microarray//qRT-PCR//Western blogFunctional MTI19688090
hsa-miR-185-5pMIMAT0000455MIRT004700CLASHFunctional MTI (Weak)23622248
hsa-miR-203aMIMAT0000264MIRT004723Luciferase reporter assay//qRT-PCR//Western blotFunctional MTI19843643
hsa-miR-191-5pMIMAT0000440MIRT006721Luciferase reporter assay//qRT-PCR//Western blotFunctional MTI22683624
hsa-miR-218-5pMIMAT0000275MIRT007145HITS-CLIP//Luciferase reporter assay//Western blotFunctional MTI23212916
hsa-miR-449b-5pMIMAT0003327MIRT016139Reporter assay;Western blotFunctional MTI19833767
hsa-miR-193b-3pMIMAT0002819MIRT016513MicroarrayFunctional MTI (Weak)20304954
hsa-miR-103a-3pMIMAT0000101MIRT027234SequencingFunctional MTI (Weak)20371350
hsa-miR-22-3pMIMAT0000077MIRT030654SequencingFunctional MTI (Weak)20371350
hsa-miR-1303MIMAT0005891MIRT035884CLASHFunctional MTI (Weak)23622248
hsa-miR-615-3pMIMAT0003283MIRT040000CLASHFunctional 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-137MIMAT00004291hsa-miR-137{Western blot}{overexpression by miRNA precursor transfection}18381414
hsa-miR-21-5pMIMAT0000076NAhsa-miR-21{Western blot}{overexpression by miRNA precursor transfection}17991735
hsa-let-7b-5pMIMAT0000063NAhsa-let-7b{Western blot}{overexpression by miRNA precursor transfection}17699775
hsa-miR-16-5pMIMAT0000069NAhsa-miR-16{Western blot}{overexpression}18701644
hsa-miR-34a-5pMIMAT0000255NAhsa-miR-34a{Western blot}{overexpression by miRNA precursor transfection}18834855
hsa-miR-125b-5pMIMAT0000423NAhsa-miR-125b{Western blot}{overexpression}19948152
hsa-miR-107MIMAT0000104NAhsa-miR-107{Western blot}{overexpression by miRNA mimics tranfection}19688090
hsa-miR-185-5pMIMAT0000455NAhsa-miR-18519688090
hsa-miR-29a-3pMIMAT0000086NAhsa-miR-29a{Western blot}{overexpression}19850741
hsa-miR-29b-3pMIMAT00001002hsa-miR-29b{Western blot}{overexpression}19850741
hsa-miR-29b-3pMIMAT00001003hsa-miR-29b{Western blot}{overexpression}19850741
hsa-miR-29b-3pMIMAT00001001hsa-miR-29b{Western blot}{overexpression}19850741
hsa-miR-195-5pMIMAT00004611hsa-miR-195{Western blot}{overexpression}19441017
hsa-miR-195-5pMIMAT00004612hsa-miR-195{Western blot}{overexpression}19441017
hsa-miR-129-5pMIMAT0000242NAhsa-miR-129-5p{Western blot}{overexpression}20404570
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6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 16 abstracts the gene occurs.


PubMed ID of the article

Sentenece the gene occurs

27206849Here, we report that activation of the cyclin-dependent kinases CDK4 and CDK6 are essential and sufficient to impair senescence induced by PML expression
27059142MicroRNA-33 promotes the replicative senescence of mouse embryonic fibroblasts by suppressing CDK6
27059142Moreover, we verified CDK6 as a direct target of microRNA-33 in mouse
27059142Silencing of CDK6 induced the premature senescence phenotype of MEFs similarly as microRNA-33, while enforced expression of CDK6 significantly reverse the senescence-induction effect of microRNA-33
27059142Taken together, our results suggested that microRNA-33 enhanced the replicative senescence of MEFs potentially by suppressing CDK6 expression
25684390Furthermore, in silico analysis identified four possible miR-433 target genes associated with cellular senescence: cyclin-dependent kinase 6 (CDK6), MAPK14, E2F3, and CDKN2A
25684390Mechanistically, we demonstrate that downregulation of p-Rb is attributable to a miR-433-dependent downregulation of CDK6, establishing it as a novel miR-433 associated gene
25255445Specifically, following siRNA knockdown, quantitative PCR, western blot analyses and chromatin immunoprecipitation (ChIP) show that NF-kappaB2 regulates the expression of CDK4 and CDK6, while RelB, through the regulation of genes such as PSMA5 and ANAPC1, regulates the stability of p21WAF1 and the tumour suppressor p53
24046371This oncogenic p16(INK4A) activity depends on inhibition of CDK4/CDK6, suggesting that in cervical cancer cells where retinoblastoma tumor suppressor is inactivated, CDK4/CDK6 activity needs to be inhibited in order for cells to survive
23576552Furthermore, we show that Cdk6 is a direct downstream target gene of YAP in the regulation of cellular senescence, and the expression of Cdk6 is through the YAP-TEAD complex
23576552Ectopic expression of Cdk6 rescued YAP knockdown-induced senescence
23576552Finally, we find that downregulation of YAP in tumor cells increases senescence in response to chemotherapeutic agents, and YAP or Cdk6 expression rescues cellular senescence
22820504The expression of p16(INK4A) was significantly increased, whereas levels of CDK4, CDK6 and p-Rb expression were decreased in the MSCs from both untreated and treated SLE patients
21047732Paradoxically, G(1)-S phase genes such as MYC, CDK4, CDK6, CCND1, and CCND2 were strongly downregulated, in line with the observed G(1) arrest
19098430In contrast, the levels of cyclin D1, CDK4 and CDK6 were sharply decreased
18843795We 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
15460900The p16INK4a tumor suppressor protein functions as an inhibitor of CDK4 and CDK6, the D-type cyclin-dependent kinases that initiate the phosphorylation of the retinoblastoma tumor suppressor protein, RB
9732051Likewise, cyclin D is complexed with its catalytic partners CDK4 and CDK6 in senescent HDF, but it is not known whether these complexes are active
9732051In contrast, p16Ink4a, which binds monomeric CDK4 and CDK6 thereby preventing their binding to cyclin D, is increased dramatically at the time of senescence and remains high for at least 2 mo
9704925There was also an increased binding of p16 to the Cdk6 kinase in senescent cells, and a decreased Cdk6 as well as Cdk2 kinase activity
9584157Cyclin D2 was also found to be associated with the cyclin-dependent kinases CDK2 and CDK4 but not CDK6 during growth arrest
9395243The p16/MTS1/CDKN2 gene on human chromosome band 9p21 encodes two unrelated proteins: p16INK4a, a specific inhibitor of the cyclin D-dependent kinases CKD4 and CDK6, and the structurally unrelated p19ARF protein that arrests cell growth in G1/S and also in G2/M
8943005To determine a possible mechanism by which senescent human fibroblasts maintain a hypophosphorylated Rb, we examined the expression levels and interaction of the Rb kinases, CDK4 and CDK6, and the cyclin-dependent kinase inhibitors p21 and p16 in senescent HDFs
8943005In senescent HDFs, p16 was shown to be complexed to both CDK4 and CDK6
8943005Immunodepletion analysis of p21 and p16 from the senescent cell extracts revealed that p16 is the major CDK inhibitor for both CDK4 and CDK6 kinases
8943005Immunoprecipitation of CDK4 and CDK6 and their associated proteins from radiolabeled extracts from senescent HDFs showed no other CDK inhibitors
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