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Gene Review

CLU  -  clusterin

Homo sapiens

Synonyms: AAG4, APO-J, APOJ, Aging-associated gene 4 protein, Apo-J, ...
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Disease relevance of CLU


Psychiatry related information on CLU


High impact information on CLU


Chemical compound and disease context of CLU


Biological context of CLU

  • Enhanced expression and accumulation of nuclear CLU/XIP8-Ku70/Ku80 complexes appears to be an important cell death signal after IR exposure [1].
  • Overexpression of nuclear CLU/XIP8 or its minimal Ku70 binding domain (120 aa of CLU/XIP8 C terminus) in nonirradiated MCF-7:WS8 cells dramatically reduced cell growth and colony-forming ability concomitant with increased G(1) cell cycle checkpoint arrest and increased cell death [1].
  • To clarify the functional role of clusterin in regulating apoptosis, we examined its expression in human colon cancer tissues and in human colon cancer cell lines [2].
  • Incubation of podocytes with MGN sera determined strong upregulation of pPKC-alpha/beta that was reverted by pre-incubation with clusterin, serum de-complementation, or protein-A treatment [4].
  • The protein was unmistakably identified as SP-40,40 or ApoJ, a cytolytic inhibitor and lipid carrier, by means of amino acid sequence and immunoreactivity with specific antibodies [19].

Anatomical context of CLU


Associations of CLU with chemical compounds

  • Clusterin is a widely expressed glycoprotein that has been paradoxically observed to have both pro- and antiapoptotic functions [2].
  • Orthovanadate blocked the fragmentation of nuclear DNA, inhibited DNA laddering, and suppressed the expression of TRPM-2, an apoptosis-associated gene [24].
  • METHODS AND RESULTS: Based on immunoexpression studies, functional development of Sertoli cells (SGP-2, androgen receptor) and Leydig cells (3 beta-hydroxysteroid dehydrogenase) was detectable at an age (35 weeks) when the testis is considered to be quiescent, and in advance of the pubertal rise in blood testosterone levels (50-60 weeks) [25].
  • ApoJ was found at the core of these deposits, and co-localized with the amyloid staining agent thioflavine-S [7].
  • Supportively, moderate levels of forced transgene-mediated CLU stable overexpression in KH OS cells could rescue them from DXR-mediated apoptosis [14].
  • Now we know that alternative transcriptional initiation, possibly driven by two distinct promoters, may produce at least two distinct CLU mRNA isoforms differing in their unique first exon, named Isoform 1 and Isoform 2 [26].

Physical interactions of CLU


Co-localisations of CLU


Regulatory relationships of CLU

  • These data support a potential therapeutic role for clusterin in enhancing chemotherapy-induced apoptosis and in promoting apoptosis in cells deficient in p21 [2].
  • Lipoproteins, ApoE, and ApoJ influence the uptake and degradation of Abeta in vitro and in vivo [31].
  • Clusterin is sensitive marker of glial reactivity in AIDS brains and its enhanced expression was not dependent on increases in GFAP [32].
  • Combined treatment of KoTCC-1 cells with radiation and AS clusterin ODN synergistically decreased plating efficacy and induced apoptotic cell death compared with either radiation or AS clusterin ODN treatment alone [33].
  • Expression of the human papillomavirus E6 protein in MCF-7 breast or RKO colon cancer cells enhanced basal CLU levels [34].

Other interactions of CLU

  • Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death [1].
  • Absent of p21, clusterin in not induced, and apoptosis is significantly inhibited [2].
  • Conversely, induction of apoptosis by expression of wild-type APC or by treatment with chemotherapy led to increased clusterin RNA and protein levels localizing to apoptotic nuclei [2].
  • The enzyme activity of the soluble MT6-MMP was inactive in the clusterin complex [21].
  • When thrombin-treated C9 was analyzed, clusterin was found to recognize the C9b fragment containing the hydrophobic membrane interaction segment [3].

Analytical, diagnostic and therapeutic context of CLU


  1. Nuclear clusterin/XIP8, an x-ray-induced Ku70-binding protein that signals cell death. Yang, C.R., Leskov, K., Hosley-Eberlein, K., Criswell, T., Pink, J.J., Kinsella, T.J., Boothman, D.A. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  2. Clusterin-mediated apoptosis is regulated by adenomatous polyposis coli and is p21 dependent but p53 independent. Chen, T., Turner, J., McCarthy, S., Scaltriti, M., Bettuzzi, S., Yeatman, T.J. Cancer Res. (2004) [Pubmed]
  3. Clusterin, the human apolipoprotein and complement inhibitor, binds to complement C7, C8 beta, and the b domain of C9. Tschopp, J., Chonn, A., Hertig, S., French, L.E. J. Immunol. (1993) [Pubmed]
  4. Glomerular clusterin is associated with PKC-alpha/beta regulation and good outcome of membranous glomerulonephritis in humans. Rastaldi, M.P., Candiano, G., Musante, L., Bruschi, M., Armelloni, S., Rimoldi, L., Tardanico, R., Cherchi, S.S., Ferrario, F., Montinaro, V., Haupt, R., Parodi, S., Carnevali, M.L., Allegri, L., Camussi, G., Gesualdo, L., Scolari, F., Ghiggeri, G.M. Kidney Int. (2006) [Pubmed]
  5. Clusterin (CLU) and prostate cancer. Rizzi, F., Bettuzzi, S. Adv. Cancer Res. (2009) [Pubmed]
  6. Clusterin (CLU) and lung cancer. Panico, F., Rizzi, F., Fabbri, L.M., Bettuzzi, S., Luppi, F. Adv. Cancer Res. (2009) [Pubmed]
  7. Association of apolipoprotein J-positive beta-amyloid plaques with dystrophic neurites in Alzheimer's disease brain. Martin-Rehrmann, M.D., Hoe, H.S., Capuani, E.M., Rebeck, G.W. Neurotoxicity research. (2005) [Pubmed]
  8. Alcohol biomarkers: clinical significance and biochemical basis. Lakshman, R., Tsutsumi, M., Ghosh, P., Takase, S., Anni, H., Nikolaeva, O., Israel, Y., Anton, R.F., Lesch, O.M., Helender, A., Eriksson, G., Jeppson, J.O., Marmillot , P., Rao, M.N. Alcohol. Clin. Exp. Res. (2001) [Pubmed]
  9. Clusterin/apolipoprotein J is associated with cortical Lewy bodies: immunohistochemical study in cases with alpha-synucleinopathies. Sasaki, K., Doh-ura, K., Wakisaka, Y., Iwaki, T. Acta Neuropathol. (2002) [Pubmed]
  10. Molecular biology of the Sertoli cell. Griswold, M.D., Morales, C., Sylvester, S.R. Oxford reviews of reproductive biology. (1988) [Pubmed]
  11. Clusterin solubility and aggregation in Creutzfeldt-Jakob disease. Freixes, M., Puig, B., Rodríguez, A., Torrejón-Escribano, B., Blanco, R., Ferrer, I. Acta Neuropathol. (2004) [Pubmed]
  12. Sulfated glycoprotein 2: new relationships of this multifunctional protein to neurodegeneration. May, P.C., Finch, C.E. Trends Neurosci. (1992) [Pubmed]
  13. Clusterin inhibits apoptosis by interacting with activated Bax. Zhang, H., Kim, J.K., Edwards, C.A., Xu, Z., Taichman, R., Wang, C.Y. Nat. Cell Biol. (2005) [Pubmed]
  14. Functional analysis of clusterin/apolipoprotein J in cellular death induced by severe genotoxic stress. Trougakos, I.P., Gonos, E.S. Ann. N. Y. Acad. Sci. (2004) [Pubmed]
  15. Depletion of clusterin in renal diseases causing nephrotic syndrome. Ghiggeri, G.M., Bruschi, M., Candiano, G., Rastaldi, M.P., Scolari, F., Passerini, P., Musante, L., Pertica, N., Caridi, G., Ferrario, F., Perfumo, F., Ponticelli, C. Kidney Int. (2002) [Pubmed]
  16. Clusterin expression is significantly enhanced in prostate cancer cells following androgen withdrawal therapy. July, L.V., Akbari, M., Zellweger, T., Jones, E.C., Goldenberg, S.L., Gleave, M.E. Prostate (2002) [Pubmed]
  17. Current status of carbohydrate deficient transferrin, total serum sialic acid, sialic acid index of apolipoprotein J and serum beta-hexosaminidase as markers for alcohol consumption. Javors, M.A., Johnson, B.A. Addiction (2003) [Pubmed]
  18. Clusterin protects the lung from leukocyte-induced injury. Heller, A.R., Fiedler, F., Braun, P., Stehr, S.N., Bödeker, H., Koch, T. Shock (2003) [Pubmed]
  19. 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. Ghiso, J., Matsubara, E., Koudinov, A., Choi-Miura, N.H., Tomita, M., Wisniewski, T., Frangione, B. Biochem. J. (1993) [Pubmed]
  20. Interaction of apolipoprotein J-amyloid beta-peptide complex with low density lipoprotein receptor-related protein-2/megalin. A mechanism to prevent pathological accumulation of amyloid beta-peptide. Hammad, S.M., Ranganathan, S., Loukinova, E., Twal, W.O., Argraves, W.S. J. Biol. Chem. (1997) [Pubmed]
  21. Clusterin, an abundant serum factor, is a possible negative regulator of MT6-MMP/MMP-25 produced by neutrophils. Matsuda, A., Itoh, Y., Koshikawa, N., Akizawa, T., Yana, I., Seiki, M. J. Biol. Chem. (2003) [Pubmed]
  22. Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin. Kounnas, M.Z., Loukinova, E.B., Stefansson, S., Harmony, J.A., Brewer, B.H., Strickland, D.K., Argraves, W.S. J. Biol. Chem. (1995) [Pubmed]
  23. Regulation of clusterin secretion and mRNA expression in astrocytes by cytokines. Zwain, I.H., Grima, J., Cheng, C.Y. Mol. Cell. Neurosci. (1994) [Pubmed]
  24. Protein tyrosine phosphatase regulation of endothelial cell apoptosis and differentiation. Yang, C., Chang, J., Gorospe, M., Passaniti, A. Cell Growth Differ. (1996) [Pubmed]
  25. Testicular changes during infantile 'quiescence' in the marmoset and their gonadotrophin dependence: a model for investigating susceptibility of the prepubertal human testis to cancer therapy? Kelnar, C.J., McKinnell, C., Walker, M., Morris, K.D., Wallace, W.H., Saunders, P.T., Fraser, H.M., Sharpe, R.M. Hum. Reprod. (2002) [Pubmed]
  26. Chapter 2: Clusterin (CLU): From one gene and two transcripts to many proteins. Rizzi, F., Coletta, M., Bettuzzi, S. Adv. Cancer Res. (2009) [Pubmed]
  27. Isolation and characterization of a novel gene CLUAP1 whose expression is frequently upregulated in colon cancer. Takahashi, M., Lin, Y.M., Nakamura, Y., Furukawa, Y. Oncogene (2004) [Pubmed]
  28. 150-kDa oxygen-regulated protein (ORP150) functions as a novel molecular chaperone in MDCK cells. Bando, Y., Ogawa, S., Yamauchi, A., Kuwabara, K., Ozawa, K., Hori, O., Yanagi, H., Tamatani, M., Tohyama, M. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  29. Clusterin (complement lysis inhibitor) forms a high density lipoprotein complex with apolipoprotein A-I in human plasma. Jenne, D.E., Lowin, B., Peitsch, M.C., Böttcher, A., Schmitz, G., Tschopp, J. J. Biol. Chem. (1991) [Pubmed]
  30. Distinct sites of production and deposition of the putative cell death marker clusterin in the human thymus. French, L.E., Sappino, A.P., Tschopp, J., Schifferli, J.A. J. Clin. Invest. (1992) [Pubmed]
  31. Influence of lipoproteins on microglial degradation of Alzheimer's amyloid beta-protein. Cole, G.M., Ard, M.D. Microsc. Res. Tech. (2000) [Pubmed]
  32. Upregulation of glial clusterin in brains of patients with AIDs. Torres-Muñoz, J.E., Redondo, M., Czeisler, C., Roberts, B., Tacoronte, N., Petito, C.K. Brain Res. (2001) [Pubmed]
  33. Enhanced radiosensitivity by inhibition of the anti-apoptotic gene clusterin using antisense oligodeoxynucleotide in a human bladder cancer model. Yamanaka, K., Gleave, M., Muramaki, M., Hara, I., Miyake, H. Oncol. Rep. (2005) [Pubmed]
  34. Repression of IR-inducible clusterin expression by the p53 tumor suppressor protein. Criswell, T., Klokov, D., Beman, M., Lavik, J.P., Boothman, D.A. Cancer Biol. Ther. (2003) [Pubmed]
  35. Human seminal clusterin (SP-40,40). Isolation and characterization. O'Bryan, M.K., Baker, H.W., Saunders, J.R., Kirszbaum, L., Walker, I.D., Hudson, P., Liu, D.Y., Glew, M.D., d'Apice, A.J., Murphy, B.F. J. Clin. Invest. (1990) [Pubmed]
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