HCSGD entry for PCNA


1. General information

Official gene symbolPCNA
Entrez ID5111
Gene full nameproliferating cell nuclear antigen
Other gene symbols
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:0000083Regulation of transcription involved in G1/S transition of mitotic cell cycleTASbiological_process
GO:0000278Mitotic cell cycleTASbiological_process
GO:0000701Purine-specific mismatch base pair DNA N-glycosylase activityIDAmolecular_function
GO:0000722Telomere maintenance via recombinationTASbiological_process
GO:0000723Telomere maintenanceTASbiological_process
GO:0005515Protein bindingIPImolecular_function
GO:0005634NucleusIDAcellular_component
GO:0005654NucleoplasmTAScellular_component
GO:0005663DNA replication factor C complexTAScellular_component
GO:0005730NucleolusIDAcellular_component
GO:0005737CytoplasmIDAcellular_component
GO:0006260DNA replicationNASbiological_process
GO:0006271DNA strand elongation involved in DNA replicationTASbiological_process
GO:0006275Regulation of DNA replicationIEAbiological_process
GO:0006281DNA repairNAS TASbiological_process
GO:0006283Transcription-coupled nucleotide-excision repairTASbiological_process
GO:0006284Base-excision repairTASbiological_process
GO:0006289Nucleotide-excision repairTASbiological_process
GO:0006297Nucleotide-excision repair, DNA gap fillingTASbiological_process
GO:0006298Mismatch repairIDAbiological_process
GO:0007507Heart developmentIEAbiological_process
GO:0008283Cell proliferationTASbiological_process
GO:0015630Microtubule cytoskeletonIDAcellular_component
GO:0019985Translesion synthesisIDAbiological_process
GO:0030337DNA polymerase processivity factor activityIEAmolecular_function
GO:0030971Receptor tyrosine kinase bindingIPImolecular_function
GO:0032077Positive regulation of deoxyribonuclease activityIDAbiological_process
GO:0032139Dinucleotide insertion or deletion bindingIDAmolecular_function
GO:0032201Telomere maintenance via semi-conservative replicationTASbiological_process
GO:0032405MutLalpha complex bindingIDAmolecular_function
GO:0033993Response to lipidIEAbiological_process
GO:0042802Identical protein bindingIPImolecular_function
GO:0043596Nuclear replication forkIDAcellular_component
GO:0043626PCNA complexIEAcellular_component
GO:0046686Response to cadmium ionIEAbiological_process
GO:0048015Phosphatidylinositol-mediated signalingNASbiological_process
GO:0070557PCNA-p21 complexIDAcellular_component
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4. Expression levels in datasets

  • Meta-analysis result

p-value upp-value downFDR upFDR down
0.67282225220.00531850230.99999024730.1480930453

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

Data sourceUp or downLog fold change
GSE11954Up0.3426314001
GSE13712_SHEARUp0.1229765383
GSE13712_STATICUp0.2290724398
GSE19018Down-0.0509558604
GSE19899_A1Down-0.9177115767
GSE19899_A2Down-1.4058713427
PubMed_21979375_A1Down-1.4171091104
PubMed_21979375_A2Down-1.1342811603
GSE35957Down-1.2439741614
GSE36640Down-1.6841304716
GSE54402Down-0.8798082049
GSE9593Down-0.9617660299
GSE43922Down-0.3199402154
GSE24585Up0.3484940514
GSE37065Up0.0307011633
GSE28863_A1Up0.1004596592
GSE28863_A2Up0.8930673077
GSE28863_A3Down-0.2881357220
GSE28863_A4Up0.3585948399
GSE48662Down-0.9119327887

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-193b-3pMIMAT0002819MIRT016528MicroarrayFunctional MTI (Weak)20304954
hsa-miR-124-3pMIMAT0000422MIRT023210Proteomics;MicroarrayFunctional MTI (Weak)18668037
hsa-miR-26b-5pMIMAT0000083MIRT030351MicroarrayFunctional MTI (Weak)19088304
hsa-miR-24-3pMIMAT0000080MIRT030631Reporter assay;Western blot;qRT-PCRFunctional MTI19748357
hsa-miR-615-3pMIMAT0003283MIRT039725CLASHFunctional MTI (Weak)23622248
hsa-miR-30a-5pMIMAT0000087MIRT049960CLASHFunctional MTI (Weak)23622248
hsa-miR-18a-5pMIMAT0000072MIRT050722CLASHFunctional MTI (Weak)23622248
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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: 34 abstracts the gene occurs.


PubMed ID of the article

Sentenece the gene occurs

26683595Following inhibition of ASPH activity, phosphorylation of glycogen synthase kinase 3beta and p16 expression were increased to promote senescence, whereas cyclin D1 and proliferating cell nuclear antigen were decreased to reduce cell proliferation
25819580DESIGN: First, the localization of SIRT6 and proliferation cell nuclear antigen (PCNA) in human cartilages was examined by immunohistochemistry
25440825Proliferating cell nuclear antigen and LC3 were positively correlated in the renal pelvis and UPJ (P <
25293814The cell cycle, electric nuclear volume and CD44 expression were evaluated using flow cytometry, and the phosphorylated H2AX (gamma-H2AX), p53, p21 and proliferating cell nuclear antigen (PCNA) levels were evaluated by Western blot analyses
25040935This PIM-1-mediated HP1gamma phosphorylation enhanced HP1gamma's capacity to bind to H3K9me3, resulting in heterochromatin formation and suppression of proliferative genes, such as CCNA2 and PCNA
24244594Moreover, 3-aminobenzamide increased senescence-associated beta-galactosidase activity, but decreased the expression of proliferating cell nuclear antigen in mouse lungs in response to CS
24008732The best characterized member of the ING family, ING1,interacts with the proliferating cell nuclear antigen (PCNA) in a UV-inducible manner
23296674We found that the absence of the proliferation markers Ki67 and PCNA combined with high density DNA damage foci (>5 gammaH2AX foci per nucleus) was the best quantitative indicator of cellular senescence
23296674In this chapter, we describe protocols for the dual immunofluorescence-based quantification of Ki67/PCNA and gammaH2AX in both fixed cells and paraffin-embedded tissues
22955272The retinoblastoma (Rb) protein mediates heterochromatin formation at the promoters of E2 transcription factor 1 (E2F1) target genes, such as proliferating cell nuclear antigen and cyclin A2 (CCNA2), and represses these genes during cellular senescence
22955272By comparing the promoter sequences of these genes, we found a novel TAAC element that is present in the cellular senescence-inhibited gene, proliferating cell nuclear antigen, and CCNA2 promoters but absent from the ARF and p27(KIP1) promoters
22952233Human DNA ligase I (hLigI) joins Okazaki fragments during DNA replication and completes excision repair via interactions with proliferating cell nuclear antigen and replication factor C (RFC)
22952233Unlike proliferating cell nuclear antigen, the interaction with RFC is regulated by hLigI phosphorylation
22819841Sublethal 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
22819841In 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
20457578We found that, in aged rats, wound healing improved in animals treated with LPA and/or ACI (relative to untreated controls), as assessed by histological analysis of reepithelialization and immunostaining for proliferating cell nuclear antigen
19782086In human EPCs, cell senescence, apoptosis and proliferation were assessed by acidic beta-gal and measurement of telomere length, TUNEL and PCNA labeling, respectively
19408652Biomarkers of senescence were assessed, including cell morphology, growth curve, life span, distribution of cell cycle and senescence associated beta-galactosidase (SA-beta-gal), and the expression of proliferating cell nuclear antigen (PCNA)
19408652The mRNA and protein level of PCNA decreased gradually during cellular senescence
19223468Human DNA ligase I (hLigI) participates in DNA replication and excision repair via an interaction with proliferating cell nuclear antigen (PCNA), a DNA sliding clamp
19223468In addition, hLigI interacts with and is inhibited by replication factor C (RFC), the clamp loader complex that loads PCNA onto DNA
18691180Phenotypic effects may result from differential effects on gene expression since ING1a increases levels of both retinoblastoma and the p16 cyclin-dependent kinase inhibitor and ING1a and ING1b have opposite effects on the expression of proliferating nuclear cell antigen (PCNA), which is required for cell growth
18691180Gene expression appears to be altered by targeting of HDAC complexes to gene promoters since INGla associates with several-fold higher levels of HDAC1 in senescent, compared to replication-competent cells and ING1 is found on the PCNA promoter by chromatin immunoprecipitation analysis
17210095Positive stain of nuclear PCNA in p53(+/+) young mice had no statistical significance compared to p53(+/+) aged mice (P>0
17016587The characteristics of proliferation and metastasis were shown by PCNA (proliferating cell nuclear antigen), and nm23 and cell cycle-related genes, such as p16, p21, p53 and pRb, were analyzed by RT-PCR and immunohistochemistry
17016587F6 cells exhibited strong positivity for PCNA and negativity for nm23
16888288The level of p16INK4a expression was negatively correlated with the level of PCNA expression
16516887Relocalization occurs concomitantly with interaction with a subset of nuclear proteins, including PCNA, p53 and several regulators of acetylation such as the p300/CBP and PCAF histone acetyltransferases (HATs), as well as the histone deacetylases HDAC1 and hSir2
15220521Although the role of p21WAF1 has been explained so far only by its interaction with CDKs and with PCNA, it has several other binding partners
15130753Replicative senescent cells showed a decreased ability to induce cell proliferation, probably due to the increased expression of the p53 protein and the decreased expression of the PCNA protein, and also showed increased expression of MMP-1, and decreased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1) and procollagen
12633936Characterisation of the interaction between WRN, the helicase/exonuclease defective in progeroid Werner's syndrome, and an essential replication factor, PCNA
12633936In this paper, we characterise the interaction between WRN and an essential replication factor, PCNA
12633936We show that wild-type WRN protein physically associates with PCNA at physiological protein concentrations in normal cells, while no association is seen in cells from patients with WS
12633936We demonstrate co-localisation of WRN and PCNA at replication factories, show that PCNA binds to two distinct functional sites on WRN, and suggest a mechanism by which association between WRN and PCNA may be regulated in cells on DNA damage and during DNA replication
11980715A p21 mutant that lacked the ability to bind proliferating cell nuclear antigen (PCNA) retained the ability to induce both ROS and permanent growth arrest
11980715All of these findings establish that p21 mediates senescence by a mechanism involving ROS accumulation which does not require either its PCNA binding or the CDK inhibitory functions shared with p16
10227381Immunocytochemical studies revealed that RPA, DNA pol-alpha, PCNA, and topo I levels are higher in the immortal cell types used in these studies
10227381In the HF cells, levels of DNA pol-alpha-cat and PCNA are higher (per mg protein) in the low-passage than in the senescent cells
10022898We also provide new evidence that p21 may play a role in inactivation of the DNA replication factor proliferating cell nuclear antigen during early senescence
9925749Cyclin D1 inhibits cell proliferation through binding to PCNA and cdk2
9925749The complexes of cyclin D1 with PCNA and cdk2 increased remarkably in senescent cells, compared with young counterparts
9925749DNA synthesis of NIH-3T3 transfectants with PCNA or cdk2 expression vectors was not inhibited by the overexpression of cyclin D1
9925749These results indicate that an excessive level of cyclin D1 represses cell proliferation by inhibiting DNA replication and cdk2 activity through the binding of cyclin D1 to PCNA and cdk2, as it does in senescent cells
9698069Polypeptides involved in proliferation and DNA repair, such as proliferating cell nuclear antigen and Ki-67, have been found within zones of expected cell senescence
8853893In addition to its inhibition of CDK enzymes and proliferating cell nuclear antigen function in DNA replication, these studies reveal a novel mechanism by which p21 mediates growth arrest: direct interaction with E2F complexes and negative regulation of E2F transcription factor activity
7566157The protein p21 is a dual inhibitor of cyclin-dependent kinases and proliferating-cell nuclear antigen (PCNA), both of which are required for passage through the cell cycle
7667293The p53 tumor-suppressor protein binds DNA and activates the expression of a 21-kDa protein that inhibits both the activity of cyclin-dependent kinases and the function of proliferating cell nuclear antigen
7615495The C-terminal region of p21SDI1/WAF1/CIP1 is involved in proliferating cell nuclear antigen binding but does not appear to be required for growth inhibition
7615495Of interest were reports that p21SDI1 also bound proliferating cell nuclear antigen (PCNA), an auxiliary protein for DNA polymerase delta, and inhibited DNA replication but not DNA repair in vitro
7615495To better understand the function of this interaction in vivo, we first determined the region of p21SDI1 that was needed for PCNA binding
7615495Site-directed mutagenesis in this region led to the identification of the PCNA binding motif RQXXMTXFYXXXR and demonstrated that mutation of either amino acid Met-147 or Phe-150 resulted in almost complete ablation of PCNA binding
7615495Interestingly, 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
7698220Human cyclin D1 forms complexes with several Cdks, with proliferating cell nuclear antigen, and with a recently discovered 21-kDa inhibitor of Cdk activity
7911228The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA
7911228In normal human cells, but not in many tumour cells, p21 exists in a quaternary complex with a cyclin, a CDK, and the proliferating-cell nuclear antigen (PCNA)
7911228Furthermore, p21 blocks the ability of PCNA to activate DNA polymerase delta, the principal replicative DNA polymerase
7911228This regulation results from a direct interaction between p21 and PCNA
7911228Thus, during p53-mediated suppression of cell proliferation, p21 and PCNA may be important for coordinating cell-cycle progression, DNA replication and repair of damaged DNA
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