Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1997 Nov 15;328(Pt 1):45–50. doi: 10.1042/bj3280045

Stress-induced transcription of the clusterin/apoJ gene.

D Michel 1, G Chatelain 1, S North 1, G Brun 1
PMCID: PMC1218885  PMID: 9359832

Abstract

Clusterin/apoJ is an intriguing gene frequently isolated by differential screening in laboratories from different areas of molecular biology, since it is overexpressed in numerous cases of degenerative diseases such as Alzheimer's disease and scrapie. While the dramatic increase of clusterin expression in injured tissues is well established, the molecular basis of the gene induction remains unclear. In this study, we have focused our attention on the only DNA region strictly conserved between clusterin gene proximal promoters from different vertebrate classes. We show that this 14-bp DNA element is specifically recognized by the HSF1 transcription factor and can mediate heat-shock-induced transcription in transient expression assays. Conversely, the avian clusterin proximal promoter, point-mutated at the level of this element, no longer transmits heat-shock activation. These findings provide a possible explanation for the high sensitivity of clusterin expression to environmental changes and allow the classification of clusterin as an extracellular version of heat-shock protein.

Full Text

The Full Text of this article is available as a PDF (391.5 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akakura K., Bruchovsky N., Rennie P. S., Coldman A. J., Goldenberg S. L., Tenniswood M., Fox K. Effects of intermittent androgen suppression on the stem cell composition and the expression of the TRPM-2 (clusterin) gene in the Shionogi carcinoma. J Steroid Biochem Mol Biol. 1996 Dec;59(5-6):501–511. doi: 10.1016/s0960-0760(96)00132-x. [DOI] [PubMed] [Google Scholar]
  2. Aronow B. J., Lund S. D., Brown T. L., Harmony J. A., Witte D. P. Apolipoprotein J expression at fluid-tissue interfaces: potential role in barrier cytoprotection. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):725–729. doi: 10.1073/pnas.90.2.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blaschuk O., Burdzy K., Fritz I. B. Purification and characterization of a cell-aggregating factor (clusterin), the major glycoprotein in ram rete testis fluid. J Biol Chem. 1983 Jun 25;258(12):7714–7720. [PubMed] [Google Scholar]
  4. Boggs L. N., Fuson K. S., Baez M., Churgay L., McClure D., Becker G., May P. C. Clusterin (Apo J) protects against in vitro amyloid-beta (1-40) neurotoxicity. J Neurochem. 1996 Sep;67(3):1324–1327. doi: 10.1046/j.1471-4159.1996.67031324.x. [DOI] [PubMed] [Google Scholar]
  5. Brown T. L., Moulton B. C., Baker V. V., Mira J., Harmony J. A. Expression of apolipoprotein J in the uterus is associated with tissue remodeling. Biol Reprod. 1995 May;52(5):1038–1049. doi: 10.1095/biolreprod52.5.1038. [DOI] [PubMed] [Google Scholar]
  6. Buttyan R., Olsson C. A., Pintar J., Chang C., Bandyk M., Ng P. Y., Sawczuk I. S. Induction of the TRPM-2 gene in cells undergoing programmed death. Mol Cell Biol. 1989 Aug;9(8):3473–3481. doi: 10.1128/mcb.9.8.3473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Buttyan R., Zakeri Z., Lockshin R., Wolgemuth D. Cascade induction of c-fos, c-myc, and heat shock 70K transcripts during regression of the rat ventral prostate gland. Mol Endocrinol. 1988 Jul;2(7):650–657. doi: 10.1210/mend-2-7-650. [DOI] [PubMed] [Google Scholar]
  8. Danik M., Chabot J. G., Hassan-Gonzalez D., Suh M., Quirion R. Localization of sulfated glycoprotein-2/clusterin mRNA in the rat brain by in situ hybridization. J Comp Neurol. 1993 Aug 8;334(2):209–227. doi: 10.1002/cne.903340205. [DOI] [PubMed] [Google Scholar]
  9. Duguid J. R., Bohmont C. W., Liu N. G., Tourtellotte W. W. Changes in brain gene expression shared by scrapie and Alzheimer disease. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7260–7264. doi: 10.1073/pnas.86.18.7260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fernandes M., Xiao H., Lis J. T. Fine structure analyses of the Drosophila and Saccharomyces heat shock factor--heat shock element interactions. Nucleic Acids Res. 1994 Jan 25;22(2):167–173. doi: 10.1093/nar/22.2.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. French L. E., Wohlwend A., Sappino A. P., Tschopp J., Schifferli J. A. Human clusterin gene expression is confined to surviving cells during in vitro programmed cell death. J Clin Invest. 1994 Feb;93(2):877–884. doi: 10.1172/JCI117043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Furlong E. E., Keon N. K., Thornton F. D., Rein T., Martin F. Expression of a 74-kDa nuclear factor 1 (NF1) protein is induced in mouse mammary gland involution. Involution-enhanced occupation of a twin NF1 binding element in the testosterone-repressed prostate message-2/clusterin promoter. J Biol Chem. 1996 Nov 22;271(47):29688–29697. doi: 10.1074/jbc.271.47.29688. [DOI] [PubMed] [Google Scholar]
  13. Guenette R. S., Corbeil H. B., Léger J., Wong K., Mézl V., Mooibroek M., Tenniswood M. Induction of gene expression during involution of the lactating mammary gland of the rat. J Mol Endocrinol. 1994 Feb;12(1):47–60. doi: 10.1677/jme.0.0120047. [DOI] [PubMed] [Google Scholar]
  14. Herbomel P., Bourachot B., Yaniv M. Two distinct enhancers with different cell specificities coexist in the regulatory region of polyoma. Cell. 1984 Dec;39(3 Pt 2):653–662. doi: 10.1016/0092-8674(84)90472-0. [DOI] [PubMed] [Google Scholar]
  15. Iversen L. L., Mortishire-Smith R. J., Pollack S. J., Shearman M. S. The toxicity in vitro of beta-amyloid protein. Biochem J. 1995 Oct 1;311(Pt 1):1–16. doi: 10.1042/bj3110001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jenne D. E., Tschopp J. Clusterin: the intriguing guises of a widely expressed glycoprotein. Trends Biochem Sci. 1992 Apr;17(4):154–159. doi: 10.1016/0968-0004(92)90325-4. [DOI] [PubMed] [Google Scholar]
  17. Jenne D. E., Tschopp J. Molecular structure and functional characterization of a human complement cytolysis inhibitor found in blood and seminal plasma: identity to sulfated glycoprotein 2, a constituent of rat testis fluid. Proc Natl Acad Sci U S A. 1989 Sep;86(18):7123–7127. doi: 10.1073/pnas.86.18.7123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kida E., Pluta R., Lossinsky A. S., Golabek A. A., Choi-Miura N. H., Wisniewski H. M., Mossakowski M. J. Complete cerebral ischemia with short-term survival in rat induced by cardiac arrest. II. Extracellular and intracellular accumulation of apolipoproteins E and J in the brain. Brain Res. 1995 Mar 20;674(2):341–346. doi: 10.1016/0006-8993(94)01467-v. [DOI] [PubMed] [Google Scholar]
  19. Kirszbaum L., Sharpe J. A., Murphy B., d'Apice A. J., Classon B., Hudson P., Walker I. D. Molecular cloning and characterization of the novel, human complement-associated protein, SP-40,40: a link between the complement and reproductive systems. EMBO J. 1989 Mar;8(3):711–718. doi: 10.1002/j.1460-2075.1989.tb03430.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kounnas M. Z., Loukinova E. B., Stefansson S., Harmony J. A., Brewer B. H., Strickland D. K., Argraves W. S. Identification of glycoprotein 330 as an endocytic receptor for apolipoprotein J/clusterin. J Biol Chem. 1995 Jun 2;270(22):13070–13075. doi: 10.1074/jbc.270.22.13070. [DOI] [PubMed] [Google Scholar]
  21. Kumar S., Vinci J. M., Pytel B. A., Baglioni C. Expression of messenger RNAs for complement inhibitors in human tissues and tumors. Cancer Res. 1993 Jan 15;53(2):348–353. [PubMed] [Google Scholar]
  22. Kyriakis J. M., Banerjee P., Nikolakaki E., Dai T., Rubie E. A., Ahmad M. F., Avruch J., Woodgett J. R. The stress-activated protein kinase subfamily of c-Jun kinases. Nature. 1994 May 12;369(6476):156–160. doi: 10.1038/369156a0. [DOI] [PubMed] [Google Scholar]
  23. Lund L. R., Rømer J., Thomasset N., Solberg H., Pyke C., Bissell M. J., Danø K., Werb Z. Two distinct phases of apoptosis in mammary gland involution: proteinase-independent and -dependent pathways. Development. 1996 Jan;122(1):181–193. doi: 10.1242/dev.122.1.181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Léger J. G., Montpetit M. L., Tenniswood M. P. Characterization and cloning of androgen-repressed mRNAs from rat ventral prostate. Biochem Biophys Res Commun. 1987 Aug 31;147(1):196–203. doi: 10.1016/s0006-291x(87)80106-7. [DOI] [PubMed] [Google Scholar]
  25. Mager W. H., De Kruijff A. J. Stress-induced transcriptional activation. Microbiol Rev. 1995 Sep;59(3):506–531. doi: 10.1128/mr.59.3.506-531.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mailhos C., Howard M. K., Latchman D. S. Heat shock protects neuronal cells from programmed cell death by apoptosis. Neuroscience. 1993 Aug;55(3):621–627. doi: 10.1016/0306-4522(93)90428-i. [DOI] [PubMed] [Google Scholar]
  27. Matsubara E., Frangione B., Ghiso J. Characterization of apolipoprotein J-Alzheimer's A beta interaction. J Biol Chem. 1995 Mar 31;270(13):7563–7567. doi: 10.1074/jbc.270.13.7563. [DOI] [PubMed] [Google Scholar]
  28. May P. C., Finch C. E. Sulfated glycoprotein 2: new relationships of this multifunctional protein to neurodegeneration. Trends Neurosci. 1992 Oct;15(10):391–396. doi: 10.1016/0166-2236(92)90190-j. [DOI] [PubMed] [Google Scholar]
  29. May P. C., Lampert-Etchells M., Johnson S. A., Poirier J., Masters J. N., Finch C. E. Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer's disease and in response to experimental lesions in rat. Neuron. 1990 Dec;5(6):831–839. doi: 10.1016/0896-6273(90)90342-d. [DOI] [PubMed] [Google Scholar]
  30. McGeer P. L., Kawamata T., Walker D. G. Distribution of clusterin in Alzheimer brain tissue. Brain Res. 1992 May 8;579(2):337–341. doi: 10.1016/0006-8993(92)90071-g. [DOI] [PubMed] [Google Scholar]
  31. Michel D., Chabot J. G., Moyse E., Danik M., Quirion R. Possible functions of a new genetic marker in central nervous system: the sulfated glycoprotein-2 (SGP-2). Synapse. 1992 Jun;11(2):105–111. doi: 10.1002/syn.890110203. [DOI] [PubMed] [Google Scholar]
  32. Michel D., Chatelain G., Herault Y., Brun G. The expression of the avian clusterin gene can be driven by two alternative promoters with distinct regulatory elements. Eur J Biochem. 1995 Apr 1;229(1):215–223. [PubMed] [Google Scholar]
  33. Michel D., Gillet G., Volovitch M., Pessac B., Calothy G., Brun G. Expression of a novel gene encoding a 51.5 kD precursor protein is induced by different retroviral oncogenes in quail neuroretinal cells. Oncogene Res. 1989;4(2):127–136. [PubMed] [Google Scholar]
  34. Michel D., Moyse E., Trembleau A., Jourdan F., Brun G. Clusterin/ApoJ expression is associated with neuronal apoptosis in the olfactory mucosa of the adult mouse. J Cell Sci. 1997 Jul;110(Pt 14):1635–1645. doi: 10.1242/jcs.110.14.1635. [DOI] [PubMed] [Google Scholar]
  35. Morimoto R. I., Sarge K. D., Abravaya K. Transcriptional regulation of heat shock genes. A paradigm for inducible genomic responses. J Biol Chem. 1992 Nov 5;267(31):21987–21990. [PubMed] [Google Scholar]
  36. Norman D. J., Feng L., Cheng S. S., Gubbay J., Chan E., Heintz N. The lurcher gene induces apoptotic death in cerebellar Purkinje cells. Development. 1995 Apr;121(4):1183–1193. doi: 10.1242/dev.121.4.1183. [DOI] [PubMed] [Google Scholar]
  37. Reddy K. B., Jin G., Karode M. C., Harmony J. A., Howe P. H. Transforming growth factor beta (TGF beta)-induced nuclear localization of apolipoprotein J/clusterin in epithelial cells. Biochemistry. 1996 May 14;35(19):6157–6163. doi: 10.1021/bi952981b. [DOI] [PubMed] [Google Scholar]
  38. Samali A., Cotter T. G. Heat shock proteins increase resistance to apoptosis. Exp Cell Res. 1996 Feb 25;223(1):163–170. doi: 10.1006/excr.1996.0070. [DOI] [PubMed] [Google Scholar]
  39. Saunders J. R., Aminian A., McRae J. L., O'Farrell K. A., Adam W. R., Murphy B. F. Clusterin depletion enhances immune glomerular injury in the isolated perfused kidney. Kidney Int. 1994 Mar;45(3):817–827. doi: 10.1038/ki.1994.108. [DOI] [PubMed] [Google Scholar]
  40. Schreiber S. S., Baudry M. Selective neuronal vulnerability in the hippocampus--a role for gene expression? Trends Neurosci. 1995 Oct;18(10):446–451. doi: 10.1016/0166-2236(95)94495-q. [DOI] [PubMed] [Google Scholar]
  41. Sensibar J. A., Sutkowski D. M., Raffo A., Buttyan R., Griswold M. D., Sylvester S. R., Kozlowski J. M., Lee C. Prevention of cell death induced by tumor necrosis factor alpha in LNCaP cells by overexpression of sulfated glycoprotein-2 (clusterin). Cancer Res. 1995 Jun 1;55(11):2431–2437. [PubMed] [Google Scholar]
  42. Senut M. C., Jazat F., Choi N. H., Lamour Y. Protein SP40,40-like Immunoreactivity in the Rat Brain: Progressive Increase With Age. Eur J Neurosci. 1992;4(10):917–928. doi: 10.1111/j.1460-9568.1992.tb00118.x. [DOI] [PubMed] [Google Scholar]
  43. Tsuruta J. K., Wong K., Fritz I. B., Griswold M. D. Structural analysis of sulphated glycoprotein 2 from amino acid sequence. Relationship to clusterin and serum protein 40,40. Biochem J. 1990 Jun 15;268(3):571–578. doi: 10.1042/bj2680571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Wong P., Borst D. E., Farber D., Danciger J. S., Tenniswood M., Chader G. J., van Veen T. Increased TRPM-2/clusterin mRNA levels during the time of retinal degeneration in mouse models of retinitis pigmentosa. Biochem Cell Biol. 1994 Sep-Oct;72(9-10):439–446. doi: 10.1139/o94-058. [DOI] [PubMed] [Google Scholar]
  45. Wong P., Taillefer D., Lakins J., Pineault J., Chader G., Tenniswood M. Molecular characterization of human TRPM-2/clusterin, a gene associated with sperm maturation, apoptosis and neurodegeneration. Eur J Biochem. 1994 May 1;221(3):917–925. doi: 10.1111/j.1432-1033.1994.tb18807.x. [DOI] [PubMed] [Google Scholar]
  46. Zimarino V., Tsai C., Wu C. Complex modes of heat shock factor activation. Mol Cell Biol. 1990 Feb;10(2):752–759. doi: 10.1128/mcb.10.2.752. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. de Silva H. V., Harmony J. A., Stuart W. D., Gil C. M., Robbins J. Apolipoprotein J: structure and tissue distribution. Biochemistry. 1990 Jun 5;29(22):5380–5389. doi: 10.1021/bi00474a025. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES