HCSGD entry for IGFBP3
1. General information
| Official gene symbol | IGFBP3 |
|---|---|
| Entrez ID | 3486 |
| Gene full name | insulin-like growth factor binding protein 3 |
| Other gene symbols | BP-53 IBP3 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0001558 | Regulation of cell growth | IEA | biological_process |
| GO:0001933 | Negative regulation of protein phosphorylation | IDA | biological_process |
| GO:0001968 | Fibronectin binding | IEA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005520 | Insulin-like growth factor binding | IEA NAS | molecular_function |
| GO:0005576 | Extracellular region | IEA NAS TAS | cellular_component |
| GO:0005615 | Extracellular space | IDA | cellular_component |
| GO:0005634 | Nucleus | IDA | cellular_component |
| GO:0006468 | Protein phosphorylation | IDA | biological_process |
| GO:0006915 | Apoptotic process | IEA | biological_process |
| GO:0008160 | Protein tyrosine phosphatase activator activity | IDA | molecular_function |
| GO:0008285 | Negative regulation of cell proliferation | IGI | biological_process |
| GO:0009968 | Negative regulation of signal transduction | NAS | biological_process |
| GO:0010906 | Regulation of glucose metabolic process | IEA | biological_process |
| GO:0014912 | Negative regulation of smooth muscle cell migration | IDA | biological_process |
| GO:0016942 | Insulin-like growth factor binding protein complex | IC | cellular_component |
| GO:0031994 | Insulin-like growth factor I binding | IPI | molecular_function |
| GO:0043065 | Positive regulation of apoptotic process | IMP | biological_process |
| GO:0043085 | Positive regulation of catalytic activity | IDA | biological_process |
| GO:0043410 | Positive regulation of MAPK cascade | IEA | biological_process |
| GO:0043568 | Positive regulation of insulin-like growth factor receptor signaling pathway | IEA | biological_process |
| GO:0044267 | Cellular protein metabolic process | TAS | biological_process |
| GO:0044342 | Type B pancreatic cell proliferation | IEA | biological_process |
| GO:0045663 | Positive regulation of myoblast differentiation | IDA | biological_process |
| GO:0046872 | Metal ion binding | NAS | molecular_function |
| GO:0048662 | Negative regulation of smooth muscle cell proliferation | IDA | biological_process |
| GO:0050790 | Regulation of catalytic activity | IDA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.8140498727 | 0.0002355876 | 0.9999902473 | 0.0269604348 |
- 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 | -0.6554860643 |
| GSE13712_SHEAR | Down | -0.2762758680 |
| GSE13712_STATIC | Down | -0.7046834080 |
| GSE19018 | Up | 1.4020028814 |
| GSE19899_A1 | Down | -3.2648354887 |
| GSE19899_A2 | Down | -2.4906380726 |
| PubMed_21979375_A1 | Down | -2.8265519747 |
| PubMed_21979375_A2 | Down | -4.5331789312 |
| GSE35957 | Down | -0.1777694640 |
| GSE36640 | Down | -0.3064838187 |
| GSE54402 | Down | -1.2156879387 |
| GSE9593 | Up | 0.2954887694 |
| GSE43922 | Down | -1.3828299731 |
| GSE24585 | Down | -0.0628228575 |
| GSE37065 | Down | -0.0933855185 |
| GSE28863_A1 | Down | -0.2234767402 |
| GSE28863_A2 | Up | 0.2248676620 |
| GSE28863_A3 | Down | -0.3206252138 |
| GSE28863_A4 | Down | -0.3358418485 |
| GSE48662 | Down | -0.1382067314 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Name | Drug | Accession number |
|---|---|---|
| Mecasermin | DB01277 | - |
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-375 | MIMAT0000728 | MIRT019713 | Microarray | Functional MTI (Weak) | 20215506 |
| hsa-miR-124-3p | MIMAT0000422 | MIRT022363 | Microarray | Functional MTI (Weak) | 18668037 |
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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-125b-5p | MIMAT0000423 | NA | hsa-miR-125b | 18056640 |
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6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 21 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 25220188 | Six genes independently correlated with either age (IL-6, TNFRSF-11B, IGFBP-3, SAA4, and COPG), prognosis (IL-6, SAA4), or the grade of the glioma (IL-6, IL-8, ICAM-1, IGFBP-3, and COPG) |
| 23991634 | The CREB-dependent reduction in RAB27A coding for the Ras-related protein Rab27A and IGFBP3 coding for the insulin-like growth factor-binding protein 3 has been confirmed for aged lung tissue, senescent fibroblasts, and lung epithelial cells on AGE-modified collagen |
| 23991634 | Our data demonstrate that the reduced protein expression of CREB might play a significant role in lung aging by modifying the transcription of RAB27A, IGFBP3, and other target genes |
| 23468063 | Following pretreatment with subcytotoxic concentrations of copper sulfate, U87-MG tumor cells showed typical aging characteristics, including reduced cell proliferation, cell enlargement, increased level of senescence-associated beta-galactosidase (SA beta-gal) activity, and overexpression of several senescence-associated genes, p16, p21, transforming growth factor beta-1 (TGF-beta1), insulin growth factor binding protein 3 (IGFBP3) and apolipoprotein J (ApoJ) |
| 22778398 | By using a secretome proteomics approach, we identified insulin-like growth factor binding protein 3 (IGFBP3) as a secreted mediator of breast cancer senescence upon chemotherapeutic drug treatment |
| 22778398 | The senescence-inducing activity of IGFBP3 is inhibited by tissue-type plasminogen activator-mediated proteolysis, which is counteracted by plasminogen activator inhibitor 1 (PAI-1), another secreted mediator of senescence |
| 22778398 | We demonstrate that IGFBP3 is a critical downstream target of PAI-1-induced senescence |
| 21677876 | Here we show that androgen deprivation therapy (ADT), a widely used treatment for advanced prostate cancer, induces a senescence-associated secretory phenotype in prostate cancer epithelial cells, indicated by increases in senescence-associated beta-galactosidase activity, heterochromatin protein 1beta foci, and expression of cathepsin B and insulin-like growth factor binding protein 3 |
| 20713685 | VAT-EC had enhanced expression of the cellular senescence markers, IGFBP3 and gamma-H2AX, and decreased expression of SIRT1 |
| 20591642 | Hormones such as leptin, ghrelin, insulin-like growth factor 1, IGFBP3, and cytokines, including IL-7, regulate both thymopoiesis and maintenance of naive T cells in the periphery |
| 19257984 | METHODS: Northern blot was used to show of the differential expression of the IGFBP-3 gene in the young and senescent 2BS cells; The size of 2 kb human IGFBP-3 upstream sequence including the series of the 5'-UTR area was amplified by PCR, and four groups of IGFBP-3 promoter fragments of different lengths were obtained by enzyme digestion |
| 19257984 | RESULTS: Compared with the young 2BS cells, the expression of the IGFBP-3 gene in the senescent 2BS cells was enhanced |
| 19257984 | There was a protein binding in the fragment site from site +59 to -58 of the IGFBP-3 enhancer |
| 19257984 | 5'-ccagcctgccaagcagcgtgccccggttgc-3' was the enhancer element of IGFBP-3 |
| 19257984 | CONCLUSION: In the 30 bp fragment from site -37 to -8 of the IGFBP-3 gene upstream, there is a new IGFBP-3 enhancer element IEE, which plays a controlling role in the expression of IGFBP-3 |
| 18171112 | Whereas insulin-like growth factor binding protein-3 (IGFBP-3) is frequently upregulated in senescent replicatively exhausted human umbilical vein endothelial cells (HUVEC), a systematic analysis of four different HUVEC donors revealed that IGFBP-3 is not consistently upregulated in all isolates at senescence |
| 18171112 | Knockdown of IGFBP-3 in senescent HUVEC by lentivirally expressed shRNA did not revert but rather enforced senescence-associated beta-galactosidase staining and apoptosis |
| 18171112 | Together the data suggest that, although IGFBP-3 acts as an anti-proliferative and premature senescence-inducing protein, the role of IGFBP-3 on senescence depends on the genetic background of the donor, and additional factors might be important to maintain the senescent phenotype |
| 17635417 | Previously, using cDNA microarray technology, we reported that expression of IGF-binding protein 3 (IGFBP3), one of the IGF-binding proteins, was increased with age in human dermal fibroblasts |
| 17635417 | The expression levels of IGFBP3 mRNA and protein were increased in HUVECs with age |
| 17635417 | Knockdown of IGFBP3 in old cells with IGFBP3 short hairpin RNA (shRNA) retrovirus resulted in the partial reduction of a variety of senescent phenotypes, such as changes in cell morphology, and decreases in population doubling times and senescence-associated beta-galactosidase (SA-beta-gal) staining |
| 17635417 | Down-regulation of IGFBP3 rescued the growth arrest induced by p53 overexpression in young HUVECs |
| 17635417 | In contrast, up-regulation of IGFBP3 in young cells and prolonged IGFBP3 treatment accelerated cellular senescence, confirmed by cell proliferation and SA-beta-gal staining |
| 17635417 | The treatment of young HUVECs with IGFBP3 repressed the levels of FOXO3a protein |
| 17635417 | Furthermore, calorie restriction reduced IGFBP3 protein levels, which were found to be increased with age in the rat liver and serum |
| 17635417 | These results suggest that IGFBP3 might play an important role in the cellular senescence of HUVECs as well as in vivo aging |
| 17451653 | Epigenetic and functional analysis of IGFBP3 and IGFBPrP1 in cellular immortalization |
| 17451653 | Overexpression of IGFBP3 or IGFBPrP1 in the immortal LFS cell lines suppressed cell growth and inhibited colony formation |
| 16504044 | In line with the gene expression we found increased cell culture supernatant concentrations of IGFBP-3 (p = 0 |
| 16504044 | The upregulation of the senescence-associated IGFBP-3 and -rP1 in emphysema suggests that inhibition of the action of insulin and insulin-like growth factors could be involved in the reduced in vitro-proliferation rate |
| 16300485 | Apoptosis resistance of senescent human fibroblasts is correlated with the absence of nuclear IGFBP-3 |
| 16300485 | IGFBP-3 accumulates in conditioned medium of senescent human fibroblasts, suggesting that it may contribute to the senescent phenotype |
| 16300485 | IGFBP-3 can enhance apoptotic cell death in tumor cells due to its ability to target intracellular regulators of apoptosis, including nuclear transcription factors |
| 16300485 | Senescent fibroblasts are highly resistant to apoptosis, suggesting that IGFBP-3 fails to induce apoptosis in this cell type; however, mechanisms of apoptosis resistance in senescent cells are poorly understood |
| 16300485 | To address this question, we studied the production and intracellular localization of IGFBP-3 in senescent fibroblasts |
| 16300485 | Whereas IGFBP-3 is highly overexpressed by senescent fibroblasts, IGFBP-3 was not detectable in the nucleus of senescent fibroblasts |
| 16300485 | The data are consistent with a model where IGFBP-3 accumulation in conditioned medium of senescent fibroblasts contributes to growth arrest of these cells, whereas the failure to endocytose IGFBP-3 and the absence of nuclear IGFBP-3 may contribute to the well-established apoptosis resistance of senescent human fibroblasts |
| 15817480 | Characterization of a novel positive transcription regulatory element that differentially regulates the insulin-like growth factor binding protein-3 (IGFBP-3) gene in senescent cells |
| 15817480 | Insulin-like growth factor binding protein-3 (IGFBP-3) is a well documented growth inhibitor and pro-apoptotic factor |
| 15817480 | IGFBP-3 mRNA and its protein are overexpressed by senescent human diploid fibroblasts |
| 15817480 | This report describes a novel transcriptional regulatory element, IGFBP-3 enhancer element (IEE), identified in the 5' untranslated region of the IGFBP-3 gene |
| 15817480 | This element differentially activates IGFBP-3 expression in senescent versus young fibroblasts |
| 15817480 | Site-directed mutagenesis within IEE abolished binding activity and selectively decreased IGFBP-3 promoter activity in senescent (but not young) cells |
| 15817480 | Furthermore, introduction of an IEE decoy suppressed the endogenous IGFBP-3 gene expression specifically in senescent cells |
| 15610763 | Genes specifically up-regulated by transdifferentiation but not by cellular senescence of PrSCs were metalloproteinase 1 tissue inhibitor (Timp1), transgelin (Tagln), gamma 2 actin (Actg2), plasminogen activator inhibitor 1 (Serpinel), insulin-like growth factor binding protein 3 (Igfbp3), parathyroid hormone-like hormone (Pthlp), Tgfb-1, four and a half LIM domains 2 (Fhl-2), hydrogen peroxide-inducible clone 5 (Hic5) and cartilage oligomeric matrix protein (Comp) |
| 15140969 | IGFBP-3, a marker of cellular senescence, is overexpressed in human papillomavirus-immortalized cervical cells and enhances IGF-1-induced mitogenesis |
| 15140969 | Human ectocervical cells, following retroviral transduction with the human papillomavirus type 16 E6/E7 oncogenes, are altered in their array of transcribed cellular genes, including increased mRNA for the insulin-like growth factor binding protein 3 (IGFBP-3) |
| 15140969 | IGFBP-3 expression is associated with cellular senescence, and its addition to many cell types inhibits growth or induces apoptosis |
| 15140969 | By immunoblotting and enzyme-linked immunosorbent assay methods, we demonstrate that late-passage, immortalized E6/E7-transduced cells secrete high levels of IGFBP-3 (25 ng/ml), which represent a 500-fold increase compared to levels in early-passage, nonimmortalized transduced cells (<0 |
| 15140969 | Consistent with a causal relationship between IGFBP-3 expression and enhanced IGF-1 responses, we found that early-passage cells could be converted to the late-passage, IGF-1-responsive phenotype by preincubation with IGFBP-3 |
| 15140969 | Thus, in contrast to findings with some cell types, IGFBP-3 expression in cervical cells is associated with augmented IGF-1 signaling and cell proliferation and correlates with the timing of cellular immortalization |
| 14580871 | TGF-beta-treated prostate epithelial cells neither showed terminal growth arrest nor induction of important senescence-relevant genes, such as p16(INK4A), IFI-6-16, IGFBP-3 or Dkk-3 |
| 12065244 | Elevated insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) mRNA in senescent human mammary epithelial cells suggested that the IGFBP-3 gene product may inhibit cell proliferation |
| 10938125 | Human papillomavirus type 16 E7 oncoprotein binds and inactivates growth-inhibitory insulin-like growth factor binding protein 3 |
| 10938125 | While it is generally assumed that this property of E7 depends on its interaction with regulators of the cell cycle, we show here that E7 targets insulin-like growth factor binding protein 3 (IGFBP-3), the product of a p53-inducible gene that is overexpressed in senescent cells |
| 10938125 | IGFBP-3 can suppress cell proliferation and induce apoptosis; we show here that IGFBP-3-mediated apoptosis is inhibited by E7, which binds to IGFBP-3 and triggers its proteolytic cleavage |
| 10938125 | Two transformation-deficient mutants of E7 failed to inactivate IGFBP-3, suggesting that inactivation of IGFBP-3 may contribute to cell transformation |
| 9080393 | Characterization of IGFBP-3, PAI-1 and SPARC mRNA expression in senescent fibroblasts |
| 9080393 | The RNA species encoded by IGFBP-3 (insulin-like growth factor binding protein-3), PAI-1 (plasminogen activator inhibitor-1) and SPARC (secreted protein-acidic and rich in cysteine; a |
| 9080393 | Characterization of the rates of transcription and the levels of message stability of these genes in early passage (young) versus late passage (old) HDF revealed that IGFBP-3, PAI-1 and SPARC are coordinately overexpressed but not regulated by a unique or simple mechanism encompassing all three transcripts |
| 7517406 | Increasing the seeding cell density of both young and old HDF led to elevated rates of IGFBP-3 secretion, an increasing ratio of the 42/38 kDa species of IGFBP-3, and degradation of all species of IGFBPs derived from both the fetal bovine serum component of the culture medium and from HDF |
| 7517406 | At a given seeding density old HDF produced more IGFBP-3 and degraded more IGFBPs than young HDF |
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