CLU

Symbol: CLU
Name: clusterin
Alias: CLI;AAG4;APOJ;KUB1;SGP2;APO-J;SGP-2;SP-40;TRPM2;TRPM-2;NA1/NA2
Entrez gene ID: 1191
Ensembl gene ID: ENSG000001
Species: Fly (Taxid: 7227)

Functional description:
The protein encoded by this gene is a secreted chaperone that can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. Alternate splicing results in both coding and non-coding variants; Isoform 1 functions as extracellular chaperone that prevents aggregation of nonnative proteins. Prevents stress- induced aggregation of blood plasma proteins. Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro). Does not require ATP. Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70. Does not refold proteins by itself. Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation. Secreted isoform 1 protects cells against apoptosis and against cytolysis by complement. Intracellular isoforms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes proteasomal degradation of COMMD1 and IKBKB. Modulates NF-kappa-B transcriptional activity. Nuclear isoforms promote apoptosis. Mitochondrial isoforms suppress BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis. Plays a role in the regulation of cell proliferation. [UniProt]

Observation:

Overexpression of the secretory form of human Clusterin in fruit flies increases mean lifespan. hClu overexpression flies also have greater tolerance to heat shock, wet starvation, and oxidative stress and the whole body amounts of reactive oxygen species is lower [22465014].CLU was found to be associated with longevity [16804001].



Assays: Organismal Lifespan

Classification:
  • Longevity-Associated


  • Type:
  • Gene
  • Protein coding

    References:
  • 16804001: Reduced expression levels of the senescence biomarker clusterin/apolipoprotein j in lymphocytes from healthy centenarians.
  • 22465014: Over-expression of human clusterin increases stress resistance and extends lifespan in Drosophila melanogaster.


  • Aging Relevance Analysis/Source:
  • GenAge
  • GenDR

  • Homologs
  • CLU (9606)
  • CLU (9598)
  • CLU (9615)
  • CLU (9913)
  • Clu (10090)
  • Clu (10116)
  • CLU (9031)
  • clu (7955)



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