1991 Oct 1;88(19):8577-81. Alzheimer’s disease (AD) is the most common form of dementia, accounting for over 60% of the 46.8 million cases worldwide. Further studies have suggested that people who already have Alzheimer's disease have more clusterin in their blood, and that clusterin levels in blood correlate with faster cognitive decline in individuals with Alzheimer's disease, but have not found that clusterin levels predicted the onset of Alzheimer's disease. Epub 2006 Dec 4. [, Zoubeidi A, Ettinger S, Beraldi E, Hadaschik B, Zardan A, Klomp LW, Nelson CC, Rennie PS, Gleave ME: Clusterin facilitates COMMD1 and I-kappaB degradation to enhance NF-kappaB activity in prostate cancer cells. 2007 Jun;6(6):1039-48. [6] CLU is a molecular chaperone responsible for aiding protein folding of secreted proteins, and its three isoforms have been differentially implicated in pro- or antiapoptotic processes. J Biochem. Apomixis is a naturally occurring mode of reproduction that results in embryo formation without the involvement of meiosis or fertilization of the egg. The blot was incubated with … Unlike most other chaperone proteins, which aid intracellular proteins, CLU is a Golgi chaperone that facilitates the folding of secreted proteins in an ATP-independent way. [, James RW, Hochstrasser AC, Borghini I, Martin B, Pometta D, Hochstrasser D: Characterization of a human high density lipoprotein-associated protein, NA1/NA2. Biochemistry. These two subunits are subsequently linked by five disulphide bonds to form an anti-parallel heterodimer [ 39 ]. 2004 Oct;14(10B):2121-7. [7][9], CLU activity is also involved in infectious diseases, such as hepatitis C. CLU is induced by the stress of hepatitis C viral infection, which disrupts glucose regulation. Product is not sterile! Epub 2009 Jan 12. 1988;1(1):73-6. Biochemistry. [5] In humans, clusterin is encoded by the CLU gene on chromosome 8. [, Kirszbaum L, Bozas SE, Walker ID: SP-40,40, a protein involved in the control of the complement pathway, possesses a unique array of disulphide bridges. 2002 Oct 18;277(42):39532-40. 1991 Nov 27;1086(3):255-60. [, Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. 14. Background Information. Epub 2003 Jan 24. [, Ranney MK, Ahmed IS, Potts KR, Craven RJ: Multiple pathways regulating the anti-apoptotic protein clusterin in breast cancer. This antibody reacts with Human, Mouse, Rat samples. Meanwhile, its downregulation allows for p53 activation, which then skews the proapoptotic:antiapoptotic ratio of present Bcl-2 family members, resulting in mitochondrial dysfunction and cell death. The first of these criteria was satisfied by a recent report that clusterin forms high-molecular-weight ‘solubilized’ complexes with heat- or reduction-stressed proteins, inhibiting their precipitation. J Biol Chem. [7][8][9], The CLU gene contains nine exons and expresses three isoforms alternatively-spliced at the first exon. [, Leskov KS, Klokov DY, Li J, Kinsella TJ, Boothman DA: Synthesis and functional analyses of nuclear clusterin, a cell death protein. [PubMed:8181474] Biochim Biophys Acta. [, Bunkenborg J, Pilch BJ, Podtelejnikov AV, Wisniewski JR: Screening for N-glycosylated proteins by liquid chromatography mass spectrometry. High-molecular complexes displaying clusterin associated with the soluble PrP were also found in male seminal fluid . Theoretical Molecular Weight: 52495: Formulation: Human native Clusterin was filtered (0.4µm) and lyophilized from 0.5mg/ml in 0.1M phosphate buffer, 0.15M NaCl pH 7.5. Interacts with a broad range of misfolded proteins, including APP, APOC2 and LYZ. [11][12][13][14] In addition to Alzheimer’s disease, CLU is involved in other neurodegenerative diseases such as Huntington disease.[8]. [, Rizzi F, Caccamo AE, Belloni L, Bettuzzi S: Clusterin is a short half-life, poly-ubiquitinated protein, which controls the fate of prostate cancer cells. Proc Natl Acad Sci U S A. Appl Theor Electrophor. J Biol Chem. Clusterin-α Antibody (M-18) is replaced by a more specific monoclonal antibody, Clusterin-α (B-5) that gives a stronger signal & more consistent results. [. 1992 Feb 3;297(1-2):70-6. [, Lewandrowski U, Moebius J, Walter U, Sickmann A: Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach. 2009 May;8(5):913-23. doi: 10.1074/mcp.M800504-MCP200. Not yet tested in other applications. J Biol Chem. Epub 2011 Apr 20. [9] The gene is highly conserved in species, and the protein is widely distributed in many tissues and organs, where it participates in a number of biological processes, including lipid transport, membrane recycling, cell adhesion, programmed cell death, and complement-mediated cell lysis. BMC Genomics. Epub 2002 Aug 9. 2000 Dec 26;39(51):15953-60. Clusterin has been suggested to have a protective role during … N-glycosylation at six glycosylation sites is the final step in the generation of mCLU which, under nonreducing conditions, has a molecular weight of 75–80 kDa ( Figure 1A) [ 40 ]. [, Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Nat Methods. Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. [, Zhang H, Kim JK, Edwards CA, Xu Z, Taichman R, Wang CY: Clusterin inhibits apoptosis by interacting with activated Bax. [, Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA: Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry. [10], CLU is a member of the small heat shock protein family and, thus, a molecular chaperone. J Biol Chem. CLU promotes cell survival by a number of means, including inhibition of BAX on the mitochondrial membrane, activation of the phosphatidylinositol 3-kinase/protein kinase B pathway, modulation of extracellularular signal-regulated kinase (ERK) 1/2 signaling and matrix metallopeptidase-9 expression, promotion of angiogenesis, and mediation of the nuclear factor kappa B (NF-κB) pathway. 2006 Jun;5(6):1493-503. 2010 Feb 5;285(6):3532-9. doi: 10.1074/jbc.M109.079566. 750704); Lane 3: 8 µg of normal human plasma; Lane 4: 40 µg of normal human plasma. In humans, clusterin is encoded by the CLU gene on chromosome 8. [, Choi NH, Mazda T, Tomita M: A serum protein SP40,40 modulates the formation of membrane attack complex of complement on erythrocytes. [, Wyatt AR, Wilson MR: Identification of human plasma proteins as major clients for the extracellular chaperone clusterin. Seed-derived progeny of an apomictic plant are genetically identical to the maternal parent. Distribution Tissue distribution: Ubiquitously expressed. In clear cell renal cell carcinoma, CLU functions to regulate ERK 1/2 signaling and matrix metallopeptidase-9 expression to promote tumor cell migration, invasion, and metastasis. [, Zhang H, Li XJ, Martin DB, Aebersold R: Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry. The precursor form has a predicted molecular mass of 60 kDa, whereas the mature glycosylated form is secreted as a protein with a molecular mass of 75–80 kDa, termed secretory clusterin (sCLU) [123, 124]. Western blot of HRP anti-Clusterin antibody (clone A15113A). 1990 Aug 25;265(24):14292-7. Biochim Biophys Acta. 2008 Sep;8(18):3833-47. doi: 10.1002/pmic.200701057. The additional lower molecular weight band detected in the ATP7B immunoblots likely represents a degradation product of ATP7B that was previously characterized . 2006 Feb;5(2):226-33. [, Yerbury JJ, Poon S, Meehan S, Thompson B, Kumita JR, Dobson CM, Wilson MR: The extracellular chaperone clusterin influences amyloid formation and toxicity by interacting with prefibrillar structures. Proc Natl Acad Sci U S A. [, Liu T, Qian WJ, Gritsenko MA, Camp DG 2nd, Monroe ME, Moore RJ, Smith RD: Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. Epub 2009 Jun 17. The particle size of PCL-PEG-ColIV nanoparticles increased from 68.0 nm to 150.4 nm after modification with ColIV. Through this function, CLU is involved in many diseases related to oxidative stress, including neurodegenerative diseas… There are no reviews for Clusterin/APOJ Antibody (NBP1-68308). Interacts with APOA1, LRP2, CLUAP1 and PON1. The enhanced interaction was not attributable to alterations in ATP7B or clusterin expression, as the levels of both proteins in cell lysates were unchanged ( Fig. Clusterin (Apolipoprotein J) is a 75-80 kDa heterodimeric glycoprotein produced by a wide array of tissues and found in most biologic fluids (PMID: 7648419; 11906815). [, Ghiso J, Matsubara E, Koudinov A, Choi-Miura NH, Tomita M, Wisniewski T, Frangione B: The cerebrospinal-fluid soluble form of Alzheimer's amyloid beta is complexed to SP-40,40 (apolipoprotein J), an inhibitor of the complement membrane-attack complex. 2009 Aug 14;284(33):21920-7. doi: 10.1074/jbc.M109.033688. After further adsorption with CLU, the particle size was 151.8 nm. 2007 Sep;1772(9):1103-11. [, Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. However, little is known about the specific mechanisms that act to suppress this process in vivo. [7][8] The nuclear isoform encodes a 49 kDa protein, while the secretory isoform, which is the main gene transcript, encodes a 75–80 kDa protein after maturation (glycosylation, secretion, and dimerization). Immunohistochemistry (Formalin/PFA-fixed paraffin-embedded sections) - Anti-Clusterin antibody (ab69644) ab69644 at 1/50 dilution staining Apolipoprotein J in human brain by Immunohistochemistry, Paraffin-embedded tissue, in the absence or presence of the immunising peptide. Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors. 2009 May;219(2):314-23. doi: 10.1002/jcp.21671. J Mol Biol. The integrity of the complexes was checked peri-odically by reanalysis using the same column. As evident by its key roles in cancer development, CLU can serve as a therapeutic target for fighting tumor growth and chemoresistance. 1992 Oct;112(4):557-61. [, Leong WF, Chow VT: Transcriptomic and proteomic analyses of rhabdomyosarcoma cells reveal differential cellular gene expression in response to enterovirus 71 infection. CLU may promote tumorigenesis by facilitating BAX-KLU70 binding and, consequently, preventing BAX from localizing to the outer mitochondrial membrane to stimulate cell death. The structure of clusterin is predicted to contain amphipathic helices, which may facilitate its association with HDL particles [122, 125]. The enhanced interaction was not attributable to alterations in ATP7B or clusterin expression, as the levels of both proteins in cell lysates were unchanged (Fig. Interacts with APOA1, LRP2, CLUAP1 and PON1. Furthermore, in the absence of the leader sequence, the expressed clusterin had a molecular weight consistent with that of the predicted holoprotein (40 kDa), suggesting a compromised post‐translational processing with diffuse distribution throughout the cytoplasm. Cell Microbiol. Through this function, CLU is involved in many diseases related to oxidative stress, including neurodegenerative diseases, cancers, inflammatory diseases, and aging. [8] In addition to the above diseases, CLU has been linked to other conditions resulting from oxidative damage, including aging, glomerulonephritis, atherosclerosis, and myocardial infarction. 2004 Feb;4(2):454-65. The additional lower molecular weight band detected in the ATP7B immunoblots likely represents a degradation product of ATP7B that was previously characterized . Nat Cell Biol. Epub 2007 Jul 4. [7][9] They also perform opposing functions: the nuclear CLU binds Ku70 to release BAX and induce apoptosis, whereas the cytosolic and secretory isoforms inhibit apoptosis. All buffers and samples were filtered (0.45 m) before use. Clusterin (CLU) is an extracellular chaperone that forms stable and soluble complexes w … Mol Cell Proteomics. 1994 May 1;221(3):917-25. 1990 Jun 5;29(22):5380-9. [, Kumita JR, Poon S, Caddy GL, Hagan CL, Dumoulin M, Yerbury JJ, Stewart EM, Robinson CV, Wilson MR, Dobson CM: The extracellular chaperone clusterin potently inhibits human lysozyme amyloid formation by interacting with prefibrillar species. Epub 2009 Dec 7. Epub 2005 Aug 21. Studies have shown that clusterin may be a useful diagnostic marker for ALCL, especially in ALK-1(-) cases. [, Kapron JT, Hilliard GM, Lakins JN, Tenniswood MP, West KA, Carr SA, Crabb JW: Identification and characterization of glycosylation sites in human serum clusterin. Clusterin is a protein of 449 amino acids with a molecular mass of 52 kD. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Interacts (via alpha chain) with XRCC6. Humphreys D. et al. J Proteome Res. Interacts with the complement complex. The Mr for dimeric RTF clusterin was CCSt found to be 94 kDa; however, the more accurate estimate (1 hour by reduced conditions suggested that sum of the … Cellular distribution: Primarily extracellular in blood plasma, cerebrospinal fluid, milk, seminal plasma and colon mucosa. [7][8][9] Overexpression of the secretory CLU isoform protects the cell from apoptosis induced by cellular stress, such as chemotherapy, radiotherapy, or androgen/estrogen depletion. [7], spherical high-density lipoprotein particle, central nervous system myelin maintenance, negative regulation of protein homooligomerization, chaperone-mediated protein complex assembly, positive regulation of tau-protein kinase activity, negative regulation of amyloid-beta formation, positive regulation of nitric oxide biosynthetic process, negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage, positive regulation of neurofibrillary tangle assembly, positive regulation of amyloid-beta formation, regulation of neuronal signal transduction, positive regulation of NF-kappaB transcription factor activity, positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process, positive regulation of tumor necrosis factor production, positive regulation of intrinsic apoptotic signaling pathway, positive regulation of proteasomal ubiquitin-dependent protein catabolic process, release of cytochrome c from mitochondria, extracellularular signal-regulated kinase, GRCh38: Ensembl release 89: ENSG00000120885, GRCm38: Ensembl release 89: ENSMUSG00000022037, "Clusterin: a key player in cancer chemoresistance and its inhibition", "Inhibition of intracellular clusterin attenuates cell death in nephropathic cystinosis", "Ram rete testis fluid contains a protein (clusterin) which influences cell-cell interactions in vitro", "Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease", "Plasma clusterin and the risk of Alzheimer disease", "Plasma Protein Appears to Be Associated With Development and Severity of Alzheimer's Disease", "Exploring functional candidate genes for genetic association in german patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma", "Risk of non-Hodgkin lymphoma in association with germline variation in complement genes", "Roles of clusterin in progression, chemoresistance and metastasis of human ovarian cancer", "Clusterin expression in cutaneous CD30-positive lymphoproliferative disorders and their histologic simulants", "Interleukin-6 affects cell death escaping mechanisms acting on Bax-Ku70-Clusterin interactions in human colon cancer progression", "Intracellular clusterin inhibits mitochondrial apoptosis by suppressing p53-activating stress signals and stabilizing the cytosolic Ku70-Bax protein complex", "Clusterin expression correlates with stage and presence of large cells in mycosis fungoides", "Hepatitis delta virus epigenetically enhances clusterin expression via histone acetylation in human hepatocellular carcinoma cells", "Challenge and promise: roles for clusterin in pathogenesis, progression and therapy of cancer", "Genome-wide association study of panic disorder in the Japanese population", https://en.wikipedia.org/w/index.php?title=Clusterin&oldid=997744631, Creative Commons Attribution-ShareAlike License, This page was last edited on 2 January 2021, at 01:07. ) and Immunohistochemistry ( Paraffin ) ( IHC ( P ) ) applications weight marker ;:. 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In embryo formation without the involvement of meiosis or fertilization of the complexes was checked by! 5 ):913-23. doi: 10.1021/pr8008012 liquid chromatography mass spectrometry the integrity of the complexes checked. And PON1 the clearance of cellular debris and apoptosis Lane 4: 40 µg of normal human plasma proteins major. Buffers and samples were filtered ( 0.45 m ) before Use 1994 May 1 ; 221 ( 3:832-9... Determined by the clusterin molecular weight user molecular weight marker kit ( aldolase, ferritin, and serum! Human clusterin ( apolipoprotein J ) is a protein of 449 amino acids with a molecular mass 52.

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