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CLU

8p21-p12 HGNC:2095 MIM.185430

Friday 8 October 2010

clusterin; complement lysis inhibitor, SP-40,40, sulfated glycoprotein 2, testosterone-repressed prostate message 2, apolipoprotein J; "complement lysis inhibitor", "sulfated glycoprotein 2", "testosterone-repressed prostate message 2", "apolipoprotein J"

Definition: Clusterin is the major secreted product of Sertoli cells and is thought to play a critical role in spermatogenesis. Clusterin was also shown to be a normal constituent of human blood.

It consists of two 40-kD chains, alpha and beta, covalently joined by disulfide bonds.

Clusterin is a member of the human complement system by directly demonstrating its presence within the S-protein-containing soluble variant of the C5b-9 complex, SC5b-9.

Clusterin is also called complement lysis inhibitor. It acts as a control mechanism of the complement cascade; specifically, it prevents the binding of a C5b-C7 complex to the membrane of the target cell and in this way inhibits complement-mediated cytolysis.

Clusterin is also involved in apoptosis regulation.

Different modes of cellular stress lead to increased CLU levels, and additionally numerous growth factors and cytokines affect the expression of the CLU gene.

APC and c-MYC, both intimately linked to the Wnt signaling pathway, have previously been shown to influence CLU levels,

Functions

The protein clusterin encoded by this gene CLU appears to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. However, the function of this protein is unknown.

Three transcript variants encoding different isoforms have been found for this gene, and one of them is secreted and processed into a mature form.

Pathology

- Genetic variations in the CLU and PICALM genes are associated with cognitive function in the oldest old. (20739100)

Expression in tumors

- Clusterin expression in follicular dentritic cell tumor (FDCT)

- Clusterin expression is associated with decreased disease-free survival of patients with colorectal carcinomas. (20497247)

- Overexpression of clusterin correlates with tumor progression, metastasis in gastric cancer. (20353268)

- Clusterin expression correlates with stage and presence of large cells in mycosis fungoides. (19289586)

References

- Clusterin is expressed in normal synoviocytes and in tenosynovial giant cell tumors of localized and diffuse types: diagnostic and histogenetic implications.
Boland JM, Folpe AL, Hornick JL, Grogg KL. Am J Surg Pathol. 2009 Aug;33(8):1225-9. PMID: 19542874

- Schepeler T, Mansilla F, Christensen LL, Orntoft TF, Andersen CL. Clusterin expression can be modulated by changes in TCF1-mediated Wnt signaling. J Mol Signal. 2007 Jul 16;2(1):6 PMID: 17634137

- Clusterin expression is associated with decreased disease-free survival of patients with colorectal carcinomas. Redondo M, Rodrigo I, Alcaide J, Tellez T, Roldan MJ, Funez R, Diaz-Martin A, Rueda A, JimĂ©nez E. Histopathology. 2010 Jun;56(7):932-6. PMID: 20497247

- Overexpression of clusterin correlates with tumor progression, metastasis in gastric cancer: a study on tissue microarrays. Bi J, Guo AL, Lai YR, Li B, Zhong JM, Wu HQ, Xie Z, He YL, Lv ZL, Lau SH, Wang Q, Huang XH, Zhang LJ, Wen JM, Guan XY. Neoplasma. 2010;57(3):191-7. PMID: 20353268

- Effects of clusterin over-expression on metastatic progression and therapy in breast cancer. Flanagan L, Whyte L, Chatterjee N, Tenniswood M. BMC Cancer. 2010 Mar 22;10:107. PMID: 20307318 [Free]