← Back to Search
Clusterin: A Role In Cell Survival In The Face Of Apoptosis?
C. Koch-Brandt, C. Morgans
Published 1996 · Biology, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
Clusterin is a multifunctional glycoprotein complex found in virtually all body fluids and on the surface of cells lining body cavities. Demonstrated and proposed functions include the transport of lipoproteins, the inhibition of complement-mediated cell lysis and the modulation of cell-cell interactions. On the basis of its elevated expression in apoptotic tissues, it was originally proposed that the protein might be casually involved in apoptosis. Here, we discuss the recent data that, in contrast to the earlier notion, suggest that clusterin expression is not enhanced, but rather is down-regulated in the cells undergoing apoptosis and that its expression in the apoptotic tissue is restricted to the vital neighboring cells. These results led to the proposal that rather than being a cell death gene, clusterin is a cell survival gene, exerting a protective function on the surviving bystander cells.
This paper references
Sulfated glycoprotein-2 expression increases in rodent brain after transient global ischemia.
P. May (1992)
The granin (chromogranin/secretogranin) family.
W. Huttner (1991)
Diagnosis and management of breast cancer
M. Lippman (1988)
SP-40,40, a newly identified normal human serum protein found in the SC5b-9 complex of complement and in the immune deposits in glomerulonephritis.
B. Murphy (1988)
Murine clusterin: molecular cloning and mRNA localization of a gene associated with epithelial differentiation processes during embryogenesis
L. French (1993)
In vivo accumulation of sulfated glycoprotein 2 mRNA in rat thymocytes upon dexamethasone-induced cell death.
S. Bettuzzi (1991)
Identification of an androgen-repressed mRNA in rat ventral prostate as coding for sulphated glycoprotein 2 by cDNA cloning and sequence analysis.
S. Bettuzzi (1989)
Glucocorticoid-induced thymocyte apoptosis is associated with endogenous endonuclease activation
A. Wyllie (1980)
Sulfated glycoprotein 2: new relationships of this multifunctional protein to neurodegeneration
P. May (1992)
Human gliomas and epileptic foci express high levels of a mRNA related to rat testicular sulfated glycoprotein 2, a purported marker of cell death.
M. Danik (1991)
Gene expression during the early phases of regression of the androgen-dependent Shionogi mouse mammary carcinoma.
P. Rennie (1988)
Distinct sites of production and deposition of the putative cell death marker clusterin in the human thymus.
L. French (1992)
Transforming growth factor-β1 is in plaques in Alzheimer and Down pathologies
E. A. V. D. Wal (1993)
Induction of the TRPM-2 gene in cells undergoing programmed death.
R. Buttyan (1989)
Androgen‐repressed messages in the rat ventral prostate
M. Montpetit (1986)
Ultrastructural studies on prostatic involution in the rat. Evidence for focal irreversible damage to epithelium, and heterophagic digestion in macrophages.
H. Helminen (1972)
Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures
C. A. Smith (1989)
Abnormalities in expression of human retinal mRNA in retinitis pigmentosa
S. E. Jones (1990)
Periodicity of DNA folding in higher order chromatin structures.
J. Filipski (1990)
SP‐40,40, a protein involved in the control of the complement pathway, possesses a unique array of disulphide bridges
L. Kirszbaum (1992)
Apolipoprotein J: a membrane policeman?
T. C. Jordan-Starck (1992)
Constitutive apical secretion of an 80-kD sulfated glycoprotein complex in the polarized epithelial Madin-Darby canine kidney cell line
J. Urban (1987)
Clusterin gene expression in the rat thymus is not modulated by dexamethasone treatment.
L. French (1994)
Dexamethasone-induced apoptosis involves cleavage of DNA to large fragments prior to internucleosomal fragmentation.
D. Brown (1993)
Novel action of carnitine: Inhibition of aggregation of dispersed cells elicited by clusterin in vitro
I. Fritz (1989)
Long-term consequence of nephrectomy.
E. Higashihara (1990)
Clusterin: the intriguing guises of a widely expressed glycoprotein.
D. Jenne (1992)
Relationship between DNA fragmentation and apoptosis in the programmed cell death in the rat prostate following castration
H. English (1989)
Lack of correspondence between mRNA expression for a putative cell death molecule (SGP-2) and neuronal cell death in the central nervous system.
G. Garden (1991)
Programmed death of autoreactive thymocytes
H. Macdonald (1990)
Essential genes that regulate apoptosis.
B. Osborne (1994)
Sulfated glycoprotein-2 mRNA in the rat brain following transient forebrain ischemia.
C. Wiessner (1993)
Molecular cloning of gp 80, a glycoprotein complex secreted by kidney cells in vitro and in vivo. A link to the reproductive system and to the complement cascade.
K. Hartmann (1991)
Apoptosis: The Molecular Basis of Cell Death
L. D. Tomei (1991)
Clusterin levels increase during neuronal development.
M. O’Bryan (1993)
Biosynthesis and molecular cloning of sulfated glycoprotein 2 secreted by rat Sertoli cells.
M. Collard (1987)
c-Myc and apoptosis.
G. Packham (1995)
Molecular cloning and characterization of the novel, human complement‐associated protein, SP‐40,40: a link between the complement and reproductive systems.
L. Kirszbaum (1989)
Controlled death (apoptosis) of normal and putative preneoplastic cells in rat liver following withdrawal of tumor promoters.
W. Bursch (1984)
Abnormal distribution of retinal clusterin in retinitis pigmentosa.
C. Jomary (1993)
Molecular regulation of apoptosis: Genetic controls on cell death
G. Williams (1993)
Dynamics of gene expression for a hippocampal glycoprotein elevated in Alzheimer's disease and in response to experimental lesions in rat
P. May (1990)
Sorting of a secretory protein (gp80) to the apical surface of Caco-2 cells.
D. Appel (1994)
Mechanisms and functions of cell death.
R. Ellis (1991)
Apoptosis: suicide, execution or murder?
S. Martin (1993)
On the molecular genetics of retinitis pigmentosa.
P. Humphries (1992)
Low Density Lipoprotein Receptor-related Protein/-Macroglobulin Receptor Mediates the Cellular Internalization and Degradation of Thrombospondin
I. Mikhailenko (1995)
The biology of cell death in tumours.
A. Wyllie (1985)
Purification and characterization of a sulfated glycoprotein secreted by Sertoli cells.
M. Griswold (1986)
Analysis of differentially expressed genes in retinitis pigmentosa retinas Altered expression of clusterin mRNA
S. E. Jones (1992)
Comparison of clusterin gene expression in normal and dystrophic human retinas.
C. Jomary (1993)
Genetic control of programmed cell death in Drosophila.
K. White (1994)
Apoptotic death in epithelial cells: cleavage of DNA to 300 and/or 50 kb fragments prior to or in the absence of internucleosomal fragmentation.
F. Oberhammer (1993)
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.
D. Jenne (1989)
Expression of porcine complement cytolysis inhibitor mRNA in cultured aortic smooth muscle cells. Changes during differentiation in vitro.
V. Diemer (1992)
Human clusterin gene expression is confined to surviving cells during in vitro programmed cell death.
L. French (1994)
Apolipoprotein J: structure and tissue distribution.
H. De Silva (1990)
Prostatic ductal system in rats: regional variation in localization of an androgen-repressed gene product, sulfated glycoprotein-2.
J. Sensibar (1991)
Activation of a Ca2+−Mg2+‐dependent endonuclease as an early event in castration‐induced prostatic cell death
N. Kyprianou (1988)
Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation.
N. Kyprianou (1990)
Gene expression in response to acute unilateral ureteral obstruction.
I. Sawczuk (1989)
Glutamate triggers internucleosomal DNA cleavage in neuronal cells.
S. Kure (1991)
Cyclic adenosine 3',5'-monophosphate negatively regulates clusterin gene expression in Leydig tumor cell lines.
O. Pignataro (1992)
Definition and incidence of apoptosis : A historical perspective
J. F. R. Kerr (1991)
Localization of sulfated glycoprotein‐2/clusterin mRNA in the rat brain by in situ hybridization
M. Danik (1993)
Adrenalectomy‐induced granule cell degeneration in the rat hippocampal dentate gyrus: Characterization of an in vivo model of controlled neuronal death
R. S. Sloviter (1993)
Cell death by apoptosis and its protective role against disease.
W. Bursch (1992)
Apoptosis and signal transduction: clues to a molecular mechanism.
S. Lee (1993)
Social controls on cell survival and cell death
M. Raff (1992)
Glycoprotein III (Clusterin, Sulfated Glycoprotein 2) in Endocrine, Nervous, and Other Tissues: Immunochemical Characterization, Subcellular Localization, and Regulation of Biosynthesis
A. Laslop (1993)
Identification of the disulfide bonds in human plasma protein SP-40,40 (apolipoprotein-J).
N. Choi-Miura (1992)
Human megakaryocytes express clusterin and package it without apolipoprotein A-1 into alpha-granules.
J. Tschopp (1993)
Cellular response to androgen depletion and repletion in the rat ventral prostate: Autoradiography and morphometric analysis
Hugh F. English (1985)
Ram rete testis fluid contains a protein (clusterin) which influences cell-cell interactions in vitro.
I. Fritz (1983)
Expression of sulfated glycoprotein 2 is associated with carcinogenesis induced by N-nitroso-N-methylurea in rat prostate and seminal vesicle.
K. Kadomatsu (1993)
Programmed cell death: Dying cells synthesize a co‐ordinated, unique set of proteins in two different episodes of cell death
A. G. Wadewitz (1988)
Programmed cell death: Apoptosis and oncogenesis
G. Williams (1991)
Expression of the complement membrane attack complex and its inhibitors in Pick disease brain
O. Yasuhara (1994)
Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation.
N. Kyprianou (1991)
Stable expression of gp80 (TRPM-2, clusterin), a secretory protein implicated in programmed cell death, in transfected BHK-21 cells.
C. Pilarsky (1993)
Apoptosis: final control point in cell biology.
G. Williams (1992)
Clusterin (SGP‐2): A multifunctional glycoprotein with regional expression in astrocytes and neurons of the adult rat brain
G. Pasinetti (1994)
The apoptosis endonucleases: cleaning up after cell death?
M. Peitsch (1994)
Platelet activation releases megakaryocyte-synthesized apolipoprotein J, a highly abundant protein in atheromatous lesions.
D. Witte (1993)
Tissue-specific toxicity : biochemical mechanisms
W. Dekant (1992)
The gene for SP-40,40, human homolog of rat sulfated glycoprotein 2, rat clusterin, and rat testosterone-repressed prostate message 2, maps to chromosome 8.
M. Purrello (1991)
Expression of a novel gene encoding a 51.5 kD precursor protein is induced by different retroviral oncogenes in quail neuroretinal cells.
D. Michel (1989)
Changes in brain gene expression shared by scrapie and Alzheimer disease.
J. Duguid (1989)
Purification and characterization of a cell-aggregating factor (clusterin), the major glycoprotein in ram rete testis fluid.
O. Blaschuk (1983)
The primary structure of glycoprotein III from bovine adrenal medullary chromaffin granules. Sequence similarity with human serum protein-40,40 and rat Sertoli cell glycoprotein.
D. Palmer (1990)
Apoptosis II: The Molecular Basis of Apoptosis in Disease
L. D. Tomei (1994)
Structural analysis of clusterin and its subunits in ram rete testis fluid.
C. Y. Cheng (1988)
Transforming growth factor-β1 induces neuronal and astrocyte genes: Tubulin α1, glial fibrillary acidic protein and clusterin
N. Laping (1994)
Self-reactive γδ T cells are eliminated in the thymus
A. Dent (1990)
The control of apoptosis in mammalian cells.
M. Collins (1993)
Identification of Glycoprotein 330 as an Endocytic Receptor for Apolipoprotein J/Clusterin (*)
M. Kounnas (1995)
Clusterin (complement lysis inhibitor) forms a high density lipoprotein complex with apolipoprotein A-I in human plasma.
D. Jenne (1991)
Genomic organization and expression of the rat TRPM-2 (clusterin) gene, a gene implicated in apoptosis.
P. Wong (1993)
This paper is referenced by
Tumor progression is accompanied by significant changes in the levels of expression of polyamine metabolism regulatory genes and clusterin (sulfated glycoprotein 2) in human prostate cancer specimens.
S. Bettuzzi (2000)
Evolution and Function of Thioester-Containing Proteins and the Complement System in the Innate Immune Response
U. Shokal (2017)
Upregulation of glial clusterin in brains of patients with AIDs
J. Torres-Muñoz (2001)
Neuroendocrine Differentiation in the Progression of Prostate Cancer: An Update on Recent Developments
V. Perrot (2012)
Localization of clusterin on freeze-preserved bull spermatozoa before and after glass wool-sephadex filtration.
N. M. Ibrahim (2001)
Reduced Expression Levels of the Senescence Biomarker Clusterin/Apolipoprotein J in Lymphocytes from Healthy Centenarians
I. Trougakos (2006)
Targeting Cell Survival Genes Using Antisense Oligonucleotides to Improve Chemo- and Hormonal-Therapies in Prostate Cancer
T. Zellweger (2002)
Ca2+ homeostasis and apoptotic resistance of neuroendocrine-differentiated prostate cancer cells
K. Vanoverberghe (2004)
Ectopic expression of clusterin/apolipoprotein J or Bcl-2 decreases the sensitivity of HaCaT cells to toxic effects of ropivacaine
Evangelos Kontargiris (2004)
Increased levels of clusterin (SGP-2) mRNA and protein accompany rat ventral prostate involution following finasteride treatment.
S. Astancolle (2000)
Apoptotic cell debris and phosphatidylserine-containing lipid vesicles induce apolipoprotein J (clusterin) gene expression in vital fibroblasts.
U. Bach (2001)
Cloning and identification of genes that associate with mammalian replicative senescence.
E. Gonos (1998)
Serum levels of the senescence biomarker clusterin/apolipoprotein J increase significantly in diabetes type II and during development of coronary heart disease or at myocardial infarction
I. Trougakos (2002)
The tumour-suppressive function of CLU is explained by its localisation and interaction with HSP60
K-A Chaiwatanasirikul (2011)
Clusterin is widely expressed in systemic anaplastic large cell lymphoma but fails to differentiate primary from secondary cutaneous anaplastic large cell lymphoma.
M. E. Lae (2002)
Effect of scrotal insulation on clusterin-positive cells in ram semen and their relationship to semen quality.
N. M. Ibrahim (2001)
Clusterin in the male reproductive tract.
M. Tenniswood (1998)
Clusterin up-regulation following sub-lethal oxidative stress and lipid peroxidation in human neuroblastoma cells
P. Strocchi (2006)
Roles of clusterin in progression, chemoresistance and metastasis of human ovarian cancer
L. Wei (2009)
Increased cell death in rat blastocysts exposed to maternal diabetes in utero and to high glucose or tumor necrosis factor-alpha in vitro.
S. Pampfer (1997)
Nuclear Translocation of a Clusterin Isoform Is Associated with Induction of Anoikis in SV40‐Immortalized Human Prostate Epithelial Cells
A. Caccamo (2003)
Central neuron–glial and glial–glial interactions following axon injury
H. Aldskogius (1998)
Antisense approaches in prostate cancer
K. Chi (2004)
Gene Expression Analysis in Combination with Clinical Parameters Is Effective in Predicting Relapse after Radical Prostatectomy
M. Brausi (2004)
Glial cell responses, complement and apolipoprotein J expression following axon injury in the neonatal rat
R. Tao (1999)
A survey of clusterin and fascin expression in sarcomas and spindle cell neoplasms: strong clusterin immunostaining is highly specific for follicular dendritic cell tumor
K. L. Grogg (2005)
Clusterin Associates Specifically with Aβ40 in Alzheimer's Disease Brain Tissue
D. Howlett (2013)
Identification of biomarkers for tumor endothelial cell proliferation through gene expression profiling
J. Hardwick (2005)
Use of antisense oligonucleotides targeting the cytoprotective gene, clusterin, to enhance androgen- and chemo-sensitivity in prostate cancer
M. Gleave (2004)
Antisense Therapy: Current Status in Prostate Cancer and Other Malignancies
M. Gleave (2002)
Effects of down-regulation of clusterin by small interference RNA on human acute myeloid leukemia cells.
X. Wang (2015)
Complementary DNA expression array analysis suggests a lower expression of signal transduction proteins and receptors in cold and hot thyroid nodules.
M. Eszlinger (2001)See more