HCSGD entry for CLU


1. General information

Official gene symbolCLU
Entrez ID1191
Gene full nameclusterin
Other gene symbolsAPO-J APOJ CLI CLU1 CLU2 KUB1 NA1/NA2 SGP-2 SGP2 SP-40 TRPM-2 TRPM2
Links to Entrez GeneLinks to Entrez Gene

2. Neighbors in the network

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This gene isn't in PPI subnetwork.

3. Gene ontology annotation

GO ID

GO term

Evidence

Category

GO:0001836Release of cytochrome c from mitochondriaICbiological_process
GO:0002576Platelet degranulationTASbiological_process
GO:0005515Protein bindingIPImolecular_function
GO:0005576Extracellular regionTAScellular_component
GO:0005615Extracellular spaceIDAcellular_component
GO:0005634NucleusIEAcellular_component
GO:0005739MitochondrionIDAcellular_component
GO:0005783Endoplasmic reticulumIEAcellular_component
GO:0005829CytosolIEAcellular_component
GO:0006629Lipid metabolic processNASbiological_process
GO:0006956Complement activationTASbiological_process
GO:0006958Complement activation, classical pathwayIEAbiological_process
GO:0007596Blood coagulationTASbiological_process
GO:0008219Cell deathIEAbiological_process
GO:0009615Response to virusIEPbiological_process
GO:0016887ATPase activityIDAmolecular_function
GO:0030168Platelet activationTASbiological_process
GO:0031012Extracellular matrixIDAcellular_component
GO:0031093Platelet alpha granule lumenTAScellular_component
GO:0031625Ubiquitin protein ligase bindingIDAmolecular_function
GO:0031966Mitochondrial membraneIEAcellular_component
GO:0032436Positive regulation of proteasomal ubiquitin-dependent protein catabolic processIMPbiological_process
GO:0032463Negative regulation of protein homooligomerizationIMPbiological_process
GO:0034366Spherical high-density lipoprotein particleIDAcellular_component
GO:0042583Chromaffin granuleIEAcellular_component
GO:0043065Positive regulation of apoptotic processIMPbiological_process
GO:0043691Reverse cholesterol transportTASbiological_process
GO:0045087Innate immune responseIEAbiological_process
GO:0048471Perinuclear region of cytoplasmIDAcellular_component
GO:0050821Protein stabilizationIDAbiological_process
GO:0051092Positive regulation of NF-kappaB transcription factor activityIMPbiological_process
GO:0051787Misfolded protein bindingIDA IPImolecular_function
GO:0051788Response to misfolded proteinIDAbiological_process
GO:0061077Chaperone-mediated protein foldingIDAbiological_process
GO:0097193Intrinsic apoptotic signaling pathwayIDAbiological_process
GO:1902230Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damageIMPbiological_process
GO:2000060Positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic processIMPbiological_process
GO:2001244Positive regulation of intrinsic apoptotic signaling pathwayIMPbiological_process
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4. Expression levels in datasets

  • Meta-analysis result

p-value upp-value downFDR upFDR down
0.27070660310.00049570310.96805643250.0411066038

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

Data sourceUp or downLog fold change
GSE11954Up1.7735378435
GSE13712_SHEARDown-1.4970800457
GSE13712_STATICDown-1.7999239206
GSE19018Down-1.1248229379
GSE19899_A1Down-0.9017296375
GSE19899_A2Down-2.3594716564
PubMed_21979375_A1Down-2.2514731370
PubMed_21979375_A2Down-1.9492706390
GSE35957Down-0.7964657760
GSE36640Up1.0539120327
GSE54402Down-0.7501805942
GSE9593Up0.3635162523
GSE43922Down-1.0712588292
GSE24585Down-0.7811399802
GSE37065Up0.2252269731
GSE28863_A1Up0.8568749167
GSE28863_A2Up0.2955979271
GSE28863_A3Up0.2496727230
GSE28863_A4Down-0.4280544426
GSE48662--

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-425-5pMIMAT0003393MIRT039321CLASHFunctional MTI (Weak)23622248
hsa-miR-18a-3pMIMAT0002891MIRT040971CLASHFunctional 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-125b-5pMIMAT0000423NAhsa-miR-125b18056640
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6. Text-mining results about the gene

Gene occurances in abstracts of cellular senescence-associated articles: 17 abstracts the gene occurs.


PubMed ID of the article

Sentenece the gene occurs

24937130ATM regulates insulin-like growth factor 1-secretory clusterin (IGF-1-sCLU) expression that protects cells against senescence
24937130Here, we show that expression of secretory clusterin (sCLU), a known pro-survival extracellular chaperone, is transcriptionally up-regulated during both RS and SIPS, but not in oncogene-induced senescence, consistent with a DNA damage-inducible mechanism
23468063Following 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)
23155386Expression of apolipoprotein J (Apo J), connective tissue growth factor (CTGF), fibronectin, and laminin were examined by real-time PCR, western blot, or ELISA experiments
23155386Exposure to 8% of CSE markedly increased the number of SA-ss-Gal positive cells to up to 82%, and the mRNA expression of Apo J, CTGF, and fibronectin by approximately 3-4 fold
23155386Treatment with 8% of CSE also increased the protein expression of Apo J and CTGF and the secretion of fibronectin and laminin
22465014Over-expression of human clusterin increases stress resistance and extends lifespan in Drosophila melanogaster
22465014Clusterin is a disulfide-linked heterodimeric glycoprotein that has been implicated in a variety of biological processes
22465014Its expression has been shown to be elevated during cellular senescence and normal aging, but it is uncertain whether clusterin protects against aging or whether its expression is a consequence of aging
22465014To investigate the functions of clusterin during organismal aging, we established transgenic Drosophila alleles to induce the expression of the secretory form of human clusterin (hClu(S)) using the Gal4/UAS system
22465014In addition, clusterin was found to prevent the inactivation of glutamine synthetase (GS) by metal-catalyzed oxidation (MCO) in vitro, and this protection was only supported by thiol-reducing equivalents, such as, DTT or GSH, and not by ascorbate (a non-thiol MCO system)
22465014Furthermore, this protection against GS inactivation by clusterin was abolished by reacting clusterin with N-ethylmaleimide, a sulfhydryl group-modifying agent
22465014Taken together, these results suggest that a disulfide-linked form of clusterin functions as an antioxidant protein via its cysteine sulfhydryl groups to reduce ROS levels and delay the organismal aging in fruit flies
22016805Apolipoprotein J/clusterin in human erythrocytes is involved in the molecular process of defected material disposal during vesiculation
20554622Levels of apolipoprotein J (Apo J), SM22, and osteonectin (SPARC) mRNA were determined by real-time PCR analysis
20554622RESULTS: TGF-beta2 increased SA-beta-Gal activity, lipid peroxidation, and the mRNA expressions of Apo J, SM22, and SPARC
19171648Expression of senescence-associated genes (apolipoprotein J [Apo J], connective tissue growth factor [CTGF], fibronectin, and SM22) was examined by real-time PCR and induction of signal transduction proteins (p21, p16, and pRb) by Western blot analysis
19171648RESULTS: H(2)O(2) markedly increased the number of SA-beta-Gal-positive cells to up to 89% and the expression of Apo J, CTGF, fibronectin, and SM22 by approximately three to fourfold
18464919In vitro data showed that exposure of human diploid fibroblasts to hexavalent chromium (Cr(VI)) resulted in premature senescence and significant upregulation of the ApoJ/CLU protein
18464919In this study we analyzed blood and urine samples from shipyard industry welders being exposed to different levels of Cr(VI) over a period of five months in order to assay in vivo the relation of ApoJ/CLU serum levels with Cr(VI)
18464919Our findings confirmed the previously reported in vitro data since reduction of Cr levels, after a worksite intervention, associated with lower levels of ApoJ/CLU serum levels
18464919We concluded that the human ApoJ/CLU gene is responsive to the acute in vivo oxidative stress induced by heavy metals such as hexavalent chromium
16955214Clusterin/Apolipoprotein J (CLU) is a cellular senescence biomarker implicated in several physiological processes
16955214In this work we have investigated CLU expression and function in human haematopoietic cells
16955214We found that early passage human T cell clones (TCC) express minimal endogenous amounts of CLU, which are significantly elevated in late passage cells
16955214Moreover, exposure of TCC to increased levels of the essential micronutrient zinc in culture resulted in intense induction of CLU
16955214Because haematopoietic cells cease proliferation following induction of terminal differentiation, we also studied the expression profile of CLU in the leukemic progenitor cell lines K562 and HL-60
16955214We found that, like TCC, both cell lines express minimal endogenous levels of CLU in their actively proliferating state
16955214However, when induced to differentiate into their distinct cell types, CLU was found to be up-regulated specifically in those cells expressing the main differentiation markers
16955214Enforced stable over-expression of CLU in K562 cells inhibited the expression of the CD14 differentiation marker and blocked differentiation to either monocytes/megacaryoblasts or to erythrocytes
16955214Overall, our results suggest that CLU is actively involved in both replicative senescence and terminal differentiation in different types of human haematopoietic cells
16827160Subsequent analysis of the expression levels of two pro-survival proteins, bcl-2 and clusterin/apolipoprotein J (CLU), in cells exposed to hypoxic conditions, revealed that although bcl-2 was up-regulated independently of the cell type, CLU was induced only in the CoCl2-treated immortalized HDFs
15236767In the current work we provide evidence that workers chronically exposed to CrVI have considerably reduced serum levels of the biomarker of senescence and cell survival, Apolipoprotein J/Clusterin (ApoJ/CLU)
15236767Moreover, we have found that both the degree and the time of exposure to CrVI associate negatively with ApoJ/CLU serum levels
15236767More specifically, treated cells were growth arrested, acquired an irregular shape, were positive to beta-galactosidase staining, accumulated oxidized proteins and over-expressed the cyclin-dependent kinase inhibitor p21 and ApoJ/CLU
12200037Clusterin/Apolipoprotein J (ApoJ) is a heterodimeric highly conserved secreted glycoprotein being expressed in a wide variety of tissues and found in all human fluids
12200037Despite being cloned since 1989, no genuine function has been attributed to ApoJ so far
12200037ApoJ gene is differentially regulated by cytokines, growth factors and stress-inducing agents, while another defining prominent and intriguing ApoJ feature is its upregulation in many severe physiological disturbances states and in several neurodegenerative conditions mostly related to advanced aging
12200037Moreover, ApoJ accumulates during the viable growth arrested cellular state of senescence, that is thought to contribute to aging and to tumorigenesis suppression; paradoxically ApoJ is also upregulated in several cases of in vivo cancer progression and tumor formation
11741605In a previous study aiming to identify genes that are differentially regulated during cellular senescence we have cloned clusterin/apolipoprotein J (Apo J), a 80 kDa secreted glycoprotein
11741605In the current report we pursue our studies and show that senescence of human diploid fibroblasts is accompanied by up-regulation of both Apo J mRNA and protein levels, but with no altered biogenesis, binding partner profile or intracellular distribution of the two Apo J forms detected
11741605To analyze the causal relationship between senescence and Apo J protein accumulation, we stably overexpressed the Apo J gene in primary as well as in SV40 T antigen-immortalized human fibroblasts and we showed no alteration of the proliferative capacity of the transduced cells
11741605Despite previous reports on tumor-derived cell lines, overexpression of Apo J in human fibroblasts did not provide protection against apoptosis or growth arrest induced by hydrogen peroxide
11741605Overall, our results suggest that Apo J overexpression does not induce senescence but it is rather a secondary consequence of the senescence phenotype
11668329Apolipoprotein J inhibits the migration, adhesion, and proliferation of vascular smooth muscle cells
11668329PURPOSE: Apolipoprotein J (ApoJ) is expressed during tissue injury and remodeling and has been implicated in vascular smooth muscle cell (VSMC) differentiation
11668329Recently, the gene for ApoJ was identified as upregulated in distal anastomotic intimal hyperplasia after prosthetic arterial grafting
11668329In this study we investigate the effect of ApoJ on VSMC migration, adhesion, proliferation, and gene expression
11668329The influence of extracellular matrix interactions on ApoJ and chemotaxis was studied in a similar way, except membranes were collagen coated
11668329Furthermore, cells were exposed to ApoJ 15 minutes before or after seeding on the coated membrane (n = 10)
11668329The influence of ApoJ on cell adhesion to collagen was assessed with cell exposure to ApoJ 15 minutes before or after seeding on a collagen-coated membrane (n = 10)
11668329The effect of ApoJ in 0
11668329RESULTS: ApoJ alone was not chemotactic for VSMCs
11668329ApoJ did not induce VSMC proliferation
11668329ApoJ alone decreased VSMC thymidine incorporation by 41
11668329Interleukin-8 and endothelin-1 were demonstrated by means of the microarray to be differentially expressed more than twofold in VSMCs that were exposed to ApoJ
11668329CONCLUSION: ApoJ is a potent inhibitor of VSMC migration, adhesion, and proliferation
11668329Therefore, ApoJ may play a role, in part, in modulating the VSMC response to injury
11302695Treating young HDFs with 150 microM H(2)O(2) once or 75 microM H(2)O(2) twice in 2 weeks causes long-term growth arrest, an enlarged morphology, activation of senescence-associated beta-galactosidase, and elevated expression of collagenase and clusterin mRNAs
11060295In this work, we show that transforming growth factor-beta1 (TGF-beta1) regulates the induction of several of these biomarkers in SIPS: cellular morphology, senescence-associated beta-galactosidase activity, increase in the steady-state level of fibronectin, apolipoprotein J, osteonectin, and SM22 mRNA
11060295In the presence of each of these antibodies, the steady-state level of fibronectin, osteonectin, apolipoprotein J, and SM22 mRNA is no more increased at 72 h after stress
9570922Construction of cDNA libraries from two conditional cell lines and application of differential screening and subtractive hybridization techniques have resulted in the cloning of eight senescence-induced genes (SGP-2/Apo J, alpha 1-procollagen, osteonectin, fibronectin, SM22, cytochrome C oxidase, GTP-alpha, and a novel gene) and a senescence-repressed gene (FRS-2)
9570922Three of these genes encode for extracellular matrix proteins, others are involved in the calcium-dependent signal transduction pathways, while the SGP-2/Apo J gene may have a cellular protective function
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