HCSGD entry for CDKN2B
1. General information
| Official gene symbol | CDKN2B |
|---|---|
| Entrez ID | 1030 |
| Gene full name | cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) |
| Other gene symbols | CDK4I INK4B MTS2 P15 TP15 p15INK4b |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0000079 | Regulation of cyclin-dependent protein serine/threonine kinase activity | IDA | biological_process |
| GO:0000086 | G2/M transition of mitotic cell cycle | IMP | biological_process |
| GO:0000278 | Mitotic cell cycle | TAS | biological_process |
| GO:0001889 | Liver development | IEA | biological_process |
| GO:0004861 | Cyclin-dependent protein serine/threonine kinase inhibitor activity | IDA NAS | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005634 | Nucleus | IDA | cellular_component |
| GO:0005737 | Cytoplasm | IDA | cellular_component |
| GO:0005829 | Cytosol | TAS | cellular_component |
| GO:0006351 | Transcription, DNA-templated | TAS | biological_process |
| GO:0006367 | Transcription initiation from RNA polymerase II promoter | TAS | biological_process |
| GO:0006469 | Negative regulation of protein kinase activity | IDA NAS | biological_process |
| GO:0007050 | Cell cycle arrest | IMP | biological_process |
| GO:0007093 | Mitotic cell cycle checkpoint | IMP | biological_process |
| GO:0007179 | Transforming growth factor beta receptor signaling pathway | TAS | biological_process |
| GO:0007568 | Aging | IEA | biological_process |
| GO:0008285 | Negative regulation of cell proliferation | IMP | biological_process |
| GO:0010467 | Gene expression | TAS | biological_process |
| GO:0014070 | Response to organic cyclic compound | IEA | biological_process |
| GO:0019901 | Protein kinase binding | IPI | molecular_function |
| GO:0030219 | Megakaryocyte differentiation | IEP | biological_process |
| GO:0030511 | Positive regulation of transforming growth factor beta receptor signaling pathway | IMP | biological_process |
| GO:0030858 | Positive regulation of epithelial cell differentiation | IEA | biological_process |
| GO:0031668 | Cellular response to extracellular stimulus | IMP | biological_process |
| GO:0031670 | Cellular response to nutrient | IMP | biological_process |
| GO:0034097 | Response to cytokine | IEA | biological_process |
| GO:0042326 | Negative regulation of phosphorylation | IDA | biological_process |
| GO:0043086 | Negative regulation of catalytic activity | IDA NAS | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | TAS | biological_process |
| GO:0048536 | Spleen development | IEA | biological_process |
| GO:0050680 | Negative regulation of epithelial cell proliferation | IMP | biological_process |
| GO:0071901 | Negative regulation of protein serine/threonine kinase activity | IDA NAS | biological_process |
| GO:2000134 | Negative regulation of G1/S transition of mitotic cell cycle | IEA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0000457619 | 0.9752480795 | 0.0188203125 | 1.0000000000 |
- 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 | -0.0585444713 |
| GSE13712_SHEAR | Up | 2.2096883553 |
| GSE13712_STATIC | Up | 1.6222578234 |
| GSE19018 | Down | -0.4643184939 |
| GSE19899_A1 | Up | 3.6598225760 |
| GSE19899_A2 | Up | 2.3669380895 |
| PubMed_21979375_A1 | Up | 2.6271049382 |
| PubMed_21979375_A2 | Up | 2.9346199137 |
| GSE35957 | Down | -0.3802649652 |
| GSE36640 | Up | 1.2267352816 |
| GSE54402 | Up | 1.4328550853 |
| GSE9593 | Up | 1.1504708740 |
| GSE43922 | Up | 2.8658589157 |
| GSE24585 | Up | 0.1342089615 |
| GSE37065 | Up | 0.1750114315 |
| GSE28863_A1 | Up | 0.0377487095 |
| GSE28863_A2 | Up | 0.2341065385 |
| GSE28863_A3 | Up | 0.0706592963 |
| GSE28863_A4 | Down | -0.0497854795 |
| GSE48662 | Up | 0.8802371429 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Not regulated by drugs
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-374b-5p | MIMAT0004955 | MIRT016027 | Sequencing | Functional MTI (Weak) | 20371350 |
| hsa-miR-375 | MIMAT0000728 | MIRT019955 | Microarray | Functional MTI (Weak) | 20215506 |
| hsa-miR-98-5p | MIMAT0000096 | MIRT027714 | Microarray | Functional MTI (Weak) | 19088304 |
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- mirRecord
No target information from mirRecord
6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 25 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 26677855 | The loci that replicated (FDR < 5%) included APOE/TOMM40 (associated with Alzheimer's disease), CDKN2B/ANRIL (implicated in the regulation of cellular senescence), ABO (tags the O blood group), and SH2B3/ATXN2 (a signaling gene that extends lifespan in Drosophila and a gene involved in neurological disease) |
| 26004298 | In gastric cancer cells, INK4/ARF locus was activated to certain extent in consequence of a decrease of H3K27me3 along it caused by EZH2 silence, which contributed substantially to an increase in the expression of p15(INK4b), p14(ARF) and p16(INK4a) and resulted in cellular senescence ultimately |
| 26004298 | Furthermore, MKN28 cells, which did not express p16(INK4a) and p21(cip), could be induced to senescence via p15(INK4b) activation and suppression of p15(INK4b) reversed senescence progression induced by EZH2 downregulated |
| 26004298 | These data unravel a crucial role of EZH2 in the regulation of INK4/ARF expression and senescence procedure in gastric cancer cells, and show that the cellular senescence could just depend on the activation of p15(INK4b)/Rb pathway, suggesting the cell-type and species specificity involved in the mechanisms of senescence inducement |
| 25273595 | The latter effect appears to be mediated by a p38-dependent phosphorylation of p53, inducing the expression of p15(Ink4b) and p21(Waf1) |
| 23770676 | Amongst them, TGF-beta ligands play a major role by regulating p15(INK4b) and p21(CIP1) |
| 23645206 | ZNF313 ubiquitinates p21(WAF1) and also destabilizes p27(KIP1) and p57(KIP2), three members of the CDK-interacting protein (CIP)/kinase inhibitor protein (KIP) family of cyclin-dependent kinase inhibitors, whereas it does not affect the stability of the inhibitor of CDK (INK4) family members, such as p16(INK4A) and p15(INK4B) |
| 22340434 | The INK4/ARF locus encodes p15(INK4b) , ARF, and p16(INK4a) genes in human chromosome 9p21, the products of which are known as common key reprogramming regulators |
| 22340434 | Compared with growing fibroblasts, the CCCTC-binding factor CTCF is remarkably up-regulated in iPS cells with silencing of the three genes in the locus and is reversely down-regulated in OIS cells with high expression of p15(INK4b) and p16(INK4a) genes |
| 21448135 | This was accompanied by the suppression of several inflammatory factors and p15(INK4B), with TSC22D1 acting as a critical effector of C/EBPbeta |
| 21310926 | The functions of Kdm2b/Jhdm1b are mediated by its silencing of p15(Ink4b) expression through active demethylation of histone H3 lysine 36 dimethyl |
| 20424117 | EGFR overexpression triggers oncogene-induced senescence, accompanied by the induction of cyclin-dependent kinase inhibitors p15(INK4B), p16(INK4A), and p21 |
| 20424117 | RNA interference directed against ZEB resulted in the induction of p15(INK4B) and p16(INK4A), reactivating the EGFR-dependent senescence program |
| 19954516 | EZH2-dependent chromatin looping controls INK4a and INK4b, but not ARF, during human progenitor cell differentiation and cellular senescence |
| 19954516 | RESULTS: We found that INK4b and INK4a, but not ARF, are upregulated following the differentiation of haematopoietic progenitor cells, in ageing fibroblasts and in senescing malignant rhabdoid tumour cells |
| 19954516 | Here, we identified a second peak of PcG binding that is located approximately 3 kb upstream of the INK4b promoter |
| 19954516 | During progenitor cell differentiation and ageing, PcG silencer EZH2 attenuates, causing loss of PRC binding and transcriptional activation of INK4b and INK4a |
| 19954516 | Down regulation of EZH2 causes release of the approximately 35 kb repressive chromatin loop and induction of both INK4a and INK4b, whereas ARF expression remains unaltered |
| 19954516 | CONCLUSION: PcG silencers bind and coordinately regulate INK4b and INK4a, but not ARF, during a variety of physiological processes |
| 18836456 | The H3K36 demethylase Jhdm1b/Kdm2b regulates cell proliferation and senescence through p15(Ink4b) |
| 18836456 | Notably, the effect of Jhdm1b on cell proliferation and cellular senescence is mediated through derepression of p15(Ink4b), as loss of p15(Ink4b) function rescues cell-proliferation defects in Jhdm1b-knockdown cells |
| 18836456 | Chromatin immunoprecipitation on ectopically expressed Jhdm1b demonstrates that Jhdm1b targets the p15(Ink4b) locus and regulates its expression in an enzymatic activity-dependent manner |
| 18836456 | Collectively, our results indicate that Jhdm1b is an H3K36 demethylase that regulates cell proliferation and senescence through p15(Ink4b) |
| 18192284 | We demonstrate that this ectopic expression of p15Ink4b extends in vivo to sites of diminished progenitor cell proliferation and developmental defects in Zeb1-null mice |
| 17664422 | MYC inactivation was associated with prototypical markers of senescence, including acidic beta-gal staining, induction of p16INK4a, and p15INK4b expression |
| 17599058 | Some of these proteins, p21(Cip1), p16(INK4a) and p15(INK4b), are coexpressed in response to antiproliferative signals such as cellular senescence resulting in cell-cycle arrest |
| 17459456 | In an initial sample of 938 (aged 65-80 years) from the EPIC study (Norfolk, UK), the rs2811712 SNP minor allele (located between the shared p16(INK4a)/ARF locus and p15(INK4b)) was associated with reduced physical impairment |
| 17316622 | Oct-1 is involved in the transcriptional repression of the p15(INK4b) gene |
| 17316622 | Here, we show that the Oct-1 binding site in the human p15(INK4b) gene promoter functions as a silencer |
| 17316622 | Oct-1 specifically interacts with this binding site in vitro and in vivo and SMRT and HDAC1 are present in the p15(INK4b) proximal promoter region |
| 17316622 | Moreover, mouse embryo fibroblasts (MEFs) lacking Oct-1 have shown significantly increased levels of p15(INK4b) protein compared to their normal counterparts |
| 17316622 | Treatment with a histone deacetylase (HDAC) inhibitor has activated the expression of p15(INK4b) in wild-type MEFs but has no effect in MEFs lacking Oct-1, suggesting that Oct-1 represses p15(INK4b) gene expression in an HDAC-dependent manner |
| 17316622 | Finally, we show that the expression of Oct-1 protein significantly decreases, whereas p15(INK4b) protein significantly increases with the cellular aging process |
| 17316622 | Taken together, these results suggest that Oct-1 is an important transcriptional repressor for p15(INK4b) gene and the transcriptional repression of the p15(INK4b) gene by Oct-1 may be one of the regulatory mechanisms of cellular senescence |
| 16380648 | Previous studies showed that ECRG1 overexpression could inhibit cell growth and induce G1 cell cycle arrest and p15(INK4b) expression by interacting with Miz-1 (Myc-interacting zinc finger protein) |
| 15610763 | TGF-beta1 induced neither expression of senescence-associated markers nor genes involved in terminal growth arrest, such as senescence-associated beta-galactosidase and cyclin-dependent kinase (cdk) inhibitors p16(Ink4A) and p21(Cip1) but increased p15(Ink4B) protein expression |
| 11781834 | We find that p53, p21(CIP1) and p15(INK4b) are transiently elevated in HPECs and HUCs at the pre-senescent growth arrest, then return to low proliferating levels at terminal senescence |
| 11781834 | Analysis of p53, p21(CIP1), p15(INK4b), p16(INK4a), and p57(KIP2) reveals altered expression in immortalized, non-tumorigenic HPV16 E6 and E7 prostate lines and in tumorigenic prostate cancer cells |
| 11695244 | Over-expression of CDKIs p15INK4b, p16INK4a and p21CIP1/WAF1 genes mediate growth arrest in human osteosarcoma cell lines |
| 11695244 | Transient expression of various CDKIs (p15INK4b, p16INK4a and p21CIP1/WAF1) in KHOS cells resulted in growth arrest and the cells failed to enter the S-phase of the cell cycle as shown by a DNA synthesis inhibition assay |
| 11283613 | Miz-1 upregulates expression of the cyclin-dependent kinases (CDK) inhibitor p15INK4b by binding to the initiator element of the p15INK4b promoter |
| 11283613 | Alleles of c-myc that are unable to bind to Miz-1 fail to inhibit accumulation of p15INK4b messenger RNA in primary cells and are, as a consequence, deficient in immortalization |
| 11103932 | While p15INK4B and its binding to both cdk4 and cdk6 increased with increasing passage, some cyclin D1-bound cdk4 and cdk6 persisted in senescent cells, whose inhibition could not be attributed to p15INK4B |
| 10851091 | Assembly and activity of the proto-oncogenic cyclin D/CDK4(6) complexes, the major driving force of G1 phase progression, is negatively regulated by a family of INK4 CDK inhibitors p16INK4a, p15INK4b, p18INK4c, and p19INK4d |
| 9244355 | Both p18INK4c and p19INK4d were widely expressed during mouse embryogenesis, but p16INK4a and p15INK4b were not readily detected prenatally |
| 9244355 | Although p15INK4b, p18INK4c and p19INK4d were demonstrated in many tissues by 4 weeks after birth, p16INK4a protein expression was restricted to the lung and spleen of older mice, with increased, more widespread mRNA expression during aging |
| 9244355 | Expression of p16INK4a and p15INK4b was induced when mouse embryos were disrupted and cultured as mouse embryo 'fibroblasts' (MEFs) |
| 9244355 | The levels of p16INK4a and p18INK4c, but not p15INK4b or p19INK4d, further increased as MEFs approached senescence |
| 8761411 | Transfection experiments with CDKN2A and CDKN2B cDNA expression vectors, using mouse A9 cells and three human malignant melanoma cell lines as recipients, provided further evidence in support of this hypothesis |
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